Affinage

METAP1

Methionine aminopeptidase 1 · UniProt P53582

Length
386 aa
Mass
43.2 kDa
Annotated
2026-06-10
59 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

METAP1 is a cobalt/zinc-dependent methionine aminopeptidase that cotranslationally removes the initiator methionine from nascent polypeptides emerging at the ribosomal tunnel exit, a processing step essential for protein maturation and cell viability (PMID:8618900, PMID:11968008). In yeast, MAP1 deletion is viable but slow-growing while the map1/map2 double null is lethal, establishing that N-terminal methionine excision is essential and shared between two MetAPs that carry partly distinct in vivo substrate specificities — MetAP1 acting as the dominant isoform with characteristic preferences for small P1' residues and reduced activity toward Met-Val and Met-Thr substrates (PMID:8618900, PMID:11811952, PMID:20521764). Human MetAP1 functionally substitutes for yeast Map1p, is required for cell proliferation and normal G2/M progression, and acts together with MetAP2 for overall viability (PMID:12144506, PMID:15962312, PMID:17114291). Catalysis depends on an active-site geometry distinct from MetAP2: the human enzyme requires three Co2+ ions for optimal activity, with His212 coordinating a third metal unique to this enzyme, and its smaller active site underlies its resistance to the MetAP2 inhibitors fumagillin and ovalicin (PMID:9177176, PMID:16274222, PMID:17929833); an N-terminal zinc-binding domain that unfolds upon zinc chelation mediates 60S ribosome association and full processing efficiency (PMID:11968008, PMID:25921012), with metal loading supplied by the GTP-dependent metallochaperone Zng1/ZNG1, which physically interacts with and transfers Zn2+/Co2+ to apo-enzyme (PMID:35584675). Ribosomal recruitment is controlled by the nascent polypeptide-associated complex (NAC), which tethers METAP1 via a flexible tail and nucleates substrate-specific multienzyme complexes that coordinate methionine excision with downstream N-terminal acetylation by NatA and NatD and N-myristoylation by NMT1, the latter triggered by METAP1-dependent exposure of the myristoylation motif (PMID:37347872, PMID:39169182, PMID:40639378, PMID:41417911). METAP1-processed N-termini also partition substrates into the Arg/N-degron pathway distinct from MetAP2 [PMID:bio_10.1101_2024.10.03.616566].

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Established that N-terminal methionine excision is an essential cellular function carried out cotranslationally by two redundant MetAPs, defining MetAP1 as a distinct eukaryotic enzyme bearing an N-terminal zinc finger absent in prokaryotes.

    Evidence Genetic deletion and complementation with immunoaffinity purification and enzymatic assay in S. cerevisiae

    PMID:8618900

    Open questions at the time
    • Did not resolve the structural basis of substrate selection
    • Mechanism of ribosome targeting not addressed
  2. 1997 High

    Defined the catalytic and pharmacological distinction between the two isoforms — MetAP1 is not inhibited by fumagillin (a MetAP2-selective agent) and cannot substitute for blocked MetAP2 — and identified Asp219 as catalytically essential via a dominant-negative active-site mutation.

    Evidence In vivo yeast growth assays with fumagillin and site-directed mutagenesis with enzymatic assay

    PMID:9177176 PMID:9367524

    Open questions at the time
    • Molecular basis of inhibitor selectivity not yet structurally explained
    • In vivo substrate spectrum unquantified
  3. 2002 High

    Demonstrated that the N-terminal zinc finger mediates 60S/80S ribosome association required for efficient processing, and that MetAP1 is the dominant in vivo methionine-excision isoform with isoform-specific cleavage preferences.

    Evidence Ribosome sedimentation profiling, zinc finger mutagenesis, and in vivo reporter processing assays in yeast deletion strains

    PMID:11811952 PMID:11968008

    Open questions at the time
    • Did not identify the ribosomal docking partner
    • How the zinc finger contacts the 60S subunit unresolved
  4. 2002 Medium

    Confirmed functional conservation between yeast and human MetAP1, validating yeast as a model for the human enzyme.

    Evidence Heterologous complementation of yeast map1 null by human MetAP1

    PMID:12144506

    Open questions at the time
    • Single complementation method without biochemical characterization of the human enzyme in this context
  5. 2003 High

    Connected MetAP1 to methionine salvage metabolism and pinned the molecular determinant of ovalicin selectivity to a single active-site residue (Thr in MetAP1 vs Ala in MetAP2).

    Evidence Genetic deletion strains with MET reporter and growth assays; bidirectional site-directed mutagenesis with in vivo inhibitor sensitivity testing

    PMID:12874831 PMID:14676204

    Open questions at the time
    • Metabolic role characterized only in yeast
    • Structural consequences of the residue swap not yet visualized
  6. 2005 High

    Resolved the structural basis of MetAP1 inhibitor resistance — a smaller active site than MetAP2 — and identified Pro-x-x-Pro motifs consistent with ribosome binding.

    Evidence X-ray crystallography of human MetAP1 with comparative structural analysis

    PMID:16274222

    Open questions at the time
    • Static structure does not capture nascent-chain engagement
    • Functional role of the Pro-x-x-Pro motifs not directly tested
  7. 2005 Medium

    Established that human MetAP1 is required for cell proliferation and that combined MetAP1/MetAP2 loss is near-lethal in human cells, recapitulating the yeast double-null phenotype.

    Evidence siRNA knockdown with proliferation assays in HUVEC and A549 cells

    PMID:15962312

    Open questions at the time
    • Mechanism linking processing to proliferation not defined
    • Off-target effects of siRNA not fully excluded
  8. 2006 High

    Linked MetAP1 catalytic activity to G2/M cell cycle progression and demonstrated on-target action of selective inhibitors through rescue by MetAP1 overexpression and substrate-processing readouts.

    Evidence Selective inhibitors, FACS cell cycle analysis, siRNA, overexpression rescue, N-terminal processing assay, and ovalicin-MetAP1 co-crystal structure

    PMID:16823043 PMID:17114291

    Open questions at the time
    • The specific substrate(s) driving the G2/M requirement not identified
    • How processing defects translate to cell cycle arrest unknown
  9. 2007 High

    Defined the unusual metal requirement of human MetAP1 — three Co2+ ions with His212 coordinating a unique third ion — distinguishing it from all other MetAP family members.

    Evidence Kinetic Co2+-activation analysis and active-site mutagenesis (H212A, H212K) with in vitro enzymatic assays

    PMID:17929833

    Open questions at the time
    • Physiological identity of the in-cell catalytic metal not settled
    • How metals are loaded onto the enzyme in vivo not addressed here
  10. 2010 High

    Systematically defined human MetAP1 substrate specificity rules (small P1' residues, disfavoring Pro at P2' and acidic residues downstream), quantitatively separating its substrate space from MetAP2.

    Evidence Combinatorial peptide library screening with kinetic analysis of individual substrates

    PMID:20521764

    Open questions at the time
    • Peptide specificity may not fully reflect cotranslational nascent-chain context
    • Endogenous substrate repertoire not enumerated
  11. 2015 Medium

    Provided structural characterization of the isolated N-terminal zinc-binding domain, confirming it folds in a zinc-dependent manner.

    Evidence NMR chemical shift assignment and EDTA perturbation of the isolated ZBD

    PMID:25921012

    Open questions at the time
    • Full domain structure not solved
    • Functional ribosome-binding role not validated in this study
  12. 2016 Medium

    Mapped in vivo co-dependence of MetAP1 and MetAP2 on M[VT]X substrates at the proteome scale and linked fumagillin sensitivity to MetAP1 levels and glutathione redox state.

    Evidence N-terminomics and proteo-transcriptomic profiling across multiple cell lines with fumagillin treatment

    PMID:27542228

    Open questions at the time
    • Mechanistic link between methionine excision and glutathione homeostasis not established
    • Single-lab proteomic dataset
  13. 2022 High

    Identified the GTP-dependent metallochaperone Zng1/ZNG1 as the in vivo source of metal for MetAP1, resolving how the apo-enzyme is loaded with Zn2+/Co2+.

    Evidence In vitro metal transfer and GTPase assays, yeast deletion genetics, and physical interaction/pulldown assays

    PMID:35584675

    Open questions at the time
    • Selectivity between Zn2+ and Co2+ delivery in cells not resolved
    • Structural basis of the transfer reaction not determined
  14. 2023 High

    Defined how METAP1 accesses the ribosome — recruitment by NAC via a flexible tail to assemble an active methionine-excision complex at the tunnel exit while sparing ER-targeted proteins.

    Evidence Cryo-EM structural studies with biochemical interaction assays and in vivo validation

    PMID:37347872

    Open questions at the time
    • How NAC discriminates cytosolic from ER substrates mechanistically not fully detailed
    • Stoichiometry and dynamics on actively translating ribosomes not resolved
  15. 2023 Medium

    Identified MetAP1 as a cisplatin-binding protein, implicating it in drug cytotoxicity through cysteine chelation.

    Evidence Competitive activity-based protein profiling with functional cytotoxicity validation

    PMID:37654507

    Open questions at the time
    • Cysteine residue(s) targeted not pinpointed in the abstract
    • Contribution to cisplatin response relative to other targets unquantified
  16. 2024 High

    Showed that NAC orchestrates assembly of sequential cotranslational multienzyme complexes, pre-positioning MetAP1 with NatA (and releasing inhibitory HYPK) to couple methionine excision to N-terminal acetylation.

    Evidence Cryo-EM structures with biochemical reconstitution and in vivo studies

    PMID:39169182

    Open questions at the time
    • How substrate sequence selects between alternative downstream enzymes not fully resolved
    • Kinetic ordering on native ribosomes inferred from reconstitution
  17. 2024 Medium

    Established cell-physiological roles of METAP1 in endothelium — antiangiogenic and proinflammatory effects modulating VEGFA and preeclampsia-related genes.

    Evidence Bidirectional gain- and loss-of-function in HUVECs with tube formation, proliferation, and gene expression assays

    PMID:39727051

    Open questions at the time
    • Whether these effects require catalytic methionine excision unknown
    • Direct molecular targets linking METAP1 to VEGFA not identified
  18. 2024 Medium

    Demonstrated that MetAP1-specific N-terminal processing partitions substrates into the UBR4-dependent Arg/N-degron pathway independently of MetAP2.

    Evidence Reporter assays and CRISPR-Cas9 MetAP2 knockout with bioinformatic substrate analysis (preprint)

    PMID:bio_10.1101_2024.10.03.616566

    Open questions at the time
    • Not yet peer-reviewed
    • Endogenous degron substrate set requires biochemical confirmation
  19. 2025 High

    Extended the cotranslational multienzyme paradigm to N-myristoylation and histone maturation — NMT1 exchanges with METAP1 after methionine excision exposes the myristoylation motif, and METAP1 cooperates with NatD for histone H2A/H4 N-terminal acetylation.

    Evidence Cryo-EM structures with biochemical reconstitution and in vivo functional studies

    PMID:40639378 PMID:41417911

    Open questions at the time
    • Regulation of enzyme exchange order on individual nascent chains not resolved
    • Determinants selecting myristoylation vs acetylation routes not fully mapped
  20. 2025 Medium

    Connected ZNG1-dependent zinc activation of METAP1 to a signaling axis — increased SAM driving PRMT5-mediated AKT methylation, mTORC2 association, and AKT activation supporting proliferation and gut barrier function.

    Evidence Co-IP, SAM metabolite measurement, mass spectrometry of SDMA, AKT localization, and proliferation assays

    PMID:40642900

    Open questions at the time
    • Mechanistic link from METAP1 activity to elevated SAM not directly established
    • Each pathway step has limited individual validation depth

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which endogenous nascent-chain substrates drive the proliferation, G2/M, and signaling phenotypes of human METAP1, and how the NAC-organized multienzyme complexes are dynamically selected on individual translating ribosomes.
  • No causal substrate identified for the proliferation/G2/M requirement
  • Selection logic among NatA/NatD/NMT1 partner complexes on native polysomes unresolved
  • In-cell physiological catalytic metal identity not settled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005840 ribosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 1
Partners
BTF3NAA40NACANMT1ZNG1
Complex memberships
NAC-METAP1-NMT1 complexNAC-METAP1-NatA cotranslational complexNAC-METAP1-NatD complexZNG1-METAP1 complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 S. cerevisiae MetAP1 (Map1p) is a methionine aminopeptidase that cotranslationally removes N-terminal methionine from nascent polypeptides; it contains an N-terminal zinc-finger domain absent in prokaryotic homologs. Deletion of MAP1 is viable but causes slow growth; the double map1/map2 null is nonviable, establishing that N-terminal methionine removal is an essential function requiring two MetAPs. Genetic deletion, complementation assay, immunoaffinity purification, enzymatic activity assay Proceedings of the National Academy of Sciences of the United States of America High 8618900
1997 Fumagillin selectively inhibits S. cerevisiae MetAP2 in vivo but does NOT inhibit MetAP1 in vivo; MetAP1 function is insufficient to substitute for MetAP2 when MetAP2 is covalently blocked by fumagillin. In vivo yeast growth assay with fumagillin, differential inhibition of MetAP1 vs MetAP2 Proceedings of the National Academy of Sciences of the United States of America High 9177176
1997 Mutation of the conserved cobalt-coordinating residue Asp219 (analogous to Asp97 in E. coli MetAP) in yeast MetAP1 to Asn reduces catalytic activity ~1000-fold and alters substrate specificity, demonstrating that Asp219 is essential for catalysis. The D219N mutant acts as a dominant negative, interfering with both wild-type MetAP1 and MetAP2 function in yeast. Site-directed mutagenesis, enzymatic activity assay, in vivo yeast growth assay Archives of biochemistry and biophysics High 9367524
2002 Yeast MetAP1 is a ribosome-associated protein that primarily associates with the 60S ribosomal subunit and 80S translational complex. The N-terminal zinc finger domain is required for this association: single point mutations in the first or second zinc finger motif disrupt association with the 60S subunit and 80S complex and reduce N-terminal methionine removal from a reporter protein from ~100% to 31–35%. Ribosome sedimentation profiling, zinc finger mutagenesis, reporter protein N-terminal processing assay Journal of cellular biochemistry High 11968008
2002 MetAP1 plays the dominant role in N-terminal methionine removal in S. cerevisiae in vivo. Both MetAP1 and MetAP2 are less efficient when the penultimate residue is Val; MetAP2 is less efficient than MetAP1 for Gly, Cys, or Thr at this position, establishing different in vivo cleavage specificities. In vivo N-terminal processing assay of mutant GST reporter proteins in map1, map2, and wild-type yeast strains Archives of biochemistry and biophysics High 11811952
2002 Human MetAP1 functionally complements yeast map1 null growth defect, demonstrating conserved function between yeast and human MetAP1 in vivo. Heterologous expression of human MetAP1 in yeast map1 null strain, complementation growth assay Protein and peptide letters Medium 12144506
2003 Yeast MetAP1 plays a significant role in methionine salvage metabolism, preventing premature activation of MET genes. In cells lacking MetAP1, excess methionine causes growth inhibition by product inhibition of MetAP2 (not MetAP1), revealing differential regulation and a functional distinction between the two isoforms. Genetic deletion strains, MET gene reporter assays, growth inhibition assays with methionine supplementation Journal of cellular biochemistry Medium 12874831
2003 A single active-site residue difference between MetAP1 and MetAP2 accounts for differential sensitivity to ovalicin: the analogous position to MetAP2 Ala362 in MetAP1 is naturally a threonine, conferring resistance. Mutating MetAP1 Thr to Ala renders MetAP1 ovalicin-sensitive, and mutating MetAP2 Ala362 to Thr confers ovalicin resistance. Yeast-based mutagenesis screen, site-directed mutagenesis, in vivo inhibitor sensitivity assay The Journal of biological chemistry High 14676204
2005 Crystal structure of human MetAP1 reveals that its active site is smaller than that of human MetAP2, explaining why ovalicin/fumagillin preferentially targets MetAP2. The N-terminal region of MetAP1 contains three Pro-x-x-Pro motifs consistent with ribosome binding. X-ray crystallography, structural comparison with MetAP2–ovalicin complex Biochemistry High 16274222
2005 siRNA-mediated knockdown of MetAP1 significantly inhibits proliferation of human umbilical vein endothelial cells (HUVEC, 70–80% inhibition) and A549 lung carcinoma cells (20–30%). Combined knockdown of MetAP1 and MetAP2 produces near-complete growth inhibition, mirroring the map1/map2 double null yeast phenotype. siRNA knockdown, cell proliferation assay Journal of cellular biochemistry Medium 15962312
2006 Ovalicin forms a low-affinity covalent adduct with the active-site histidine of human MetAP1 (His310), analogous to the covalent modification of His231 in MetAP2, but with different inhibitor alignment. Several active-site residues must shift outward to accommodate the inhibitor, explaining the lower affinity for MetAP1. X-ray crystallography at 1.1 Å resolution of ovalicin–MetAP1 complex Protein science High 16823043
2006 Human MetAP1 (HsMetAP1) is required for normal G2/M phase cell cycle progression. Selective MetAP1 inhibitors (pyridine-2-carboxylic acid class) cause G2/M accumulation in tumor cells, induce apoptosis in leukemia lines, and cause N-terminal methionine retention in a known MetAP substrate. Overexpression of HsMetAP1 (but not MetAP2) confers resistance, and siRNA knockdown of HsMetAP1 recapitulates slow G2/M progression. Enzymatic assay, X-ray crystallography, cell cycle FACS analysis, siRNA knockdown, overexpression rescue, N-terminal processing assay Proceedings of the National Academy of Sciences of the United States of America High 17114291
2007 Human cytosolic MetAP1 requires at least three Co2+ ions for optimal catalysis (Hill coefficient n≈2.9). The conserved residue His212 coordinates a third Co2+ ion unique to this enzyme; H212A and H212K mutations reduce kcat 60- and 1800-fold respectively, increase K0.5 for Co2+, and decrease cooperativity, establishing that three metal ions are functionally required—more than any other MetAP family member. Kinetic analysis, site-directed mutagenesis, Co2+-activation curves, in vitro enzymatic assay Biochemistry High 17929833
2010 Systematic profiling of human MetAP1 substrate specificity using a combinatorial peptide library and kinetic analysis reveals: MetAP1 requires small residues (Gly, Ala, Ser, Cys, Pro, Thr, Val) at P1'; has lower activity toward Met-Val and Met-Thr substrates compared with MetAP2; is poorly active toward peptides with Pro at P2'; and disfavors acidic residues at P2'–P5'. Combinatorial peptide library screening, kinetic analysis of individual peptide substrates Biochemistry High 20521764
2015 The N-terminal zinc-binding domain (ZBD, residues 1–83) of human MetAP1 contains two α-helical fragments (residues 44–49 and 59–82) and unfolds upon EDTA chelation of zinc, as demonstrated by NMR chemical shift assignments. NMR spectroscopy (15N-HSQC, chemical shift assignment), EDTA perturbation Biomolecular NMR assignments Medium 25921012
2016 Both MetAP1 and MetAP2 are required in vivo for N-terminal methionine excision from M[VT]X-class substrates. Cell sensitivity to fumagillin (MetAP2 inhibitor) correlates with MetAP1 protein levels and with the ability to modulate glutathione homeostasis; fumagillin-sensitive cells show glutathione redox alterations absent in resistant cells. Large-scale N-terminus proteomics (N-terminomics), fumagillin treatment in multiple cell lines, proteo-transcriptomic analysis Oncotarget Medium 27542228
2022 Zng1 (human ortholog conserved) is a GTP-dependent metallochaperone that transfers Zn2+ or Co2+ to apo-MetAP1 (Map1p) in vitro, requiring GTP hydrolysis for metal transfer—unlike known copper chaperones. Deletion of ZNG1 in yeast causes defective Map1p function; Zng1 physically interacts with Map1p. In vitro metal transfer assay, GTPase assay, yeast deletion genetics, pulldown interaction assay, proteomics Cell reports High 35584675
2023 In eukaryotes, the nascent polypeptide-associated complex (NAC) controls ribosome binding of METAP1. NAC recruits METAP1 via a long flexible tail and provides a platform for formation of an active methionine excision complex at the ribosomal tunnel exit, ensuring efficient methionine excision from cytosolic proteins while sparing ER-targeted proteins. Biochemical interaction assays, structural studies (cryo-EM), in vivo functional studies Science High 37347872
2023 MetAP1 is a novel cisplatin-binding protein: cisplatin binds to MetAP1 via cysteine chelation and contributes to cisplatin's cytotoxicity, as demonstrated by competitive activity-based protein profiling and functional validation. Competitive activity-based protein profiling (ABPP), functional cytotoxicity validation RSC chemical biology Medium 37654507
2024 NAC assembles a multienzyme complex with MetAP1 and NatA early during translation, pre-positioning the active sites of both enzymes for sequential cotranslational processing (methionine excision then N-terminal acetylation) of nascent proteins. NAC also releases inhibitory interactions from the NatA regulatory protein HYPK to activate NatA on the ribosome. Biochemical assays, cryo-EM structural studies, in vivo studies Nature High 39169182
2024 METAP1 overexpression in human umbilical vein endothelial cells decreases tube formation (66%) and cell proliferation (72%), decreases VEGFA expression, and increases expression of preeclampsia-related genes (FLT1, INHBA, IL1B). METAP1 knockdown produces opposite effects, establishing antiangiogenic and proinflammatory roles in endothelial cells. Gain- and loss-of-function genetic approaches in HUVECs, tube formation assay, proliferation assay, gene expression analysis Circulation research Medium 39727051
2025 Human NMT1 exchanges with METAP1 at the ribosomal tunnel exit to form an active cotranslational complex together with NAC. NMT1 binding is sequence-selective and triggered by methionine excision by METAP1, which exposes the N-myristoylation motif in the nascent chain, enabling sequential cotranslational N-myristoylation. Biochemical interaction assays, cryo-EM structural studies, in vivo functional studies Molecular cell High 40639378
2025 NAC recruits MetAP1 and NatD (NAA40) to ribosomes to form a multienzyme complex for sequential cotranslational modification of histones H2A and H4: MetAP1 excises the initiator methionine, then NatD acetylates the exposed N-terminus. MetAP1 and NatD cooperate in a confined ribosomal environment to enable efficient histone maturation. Cryo-EM structural studies, biochemical assays Science advances High 41417911
2025 Zinc activates MetAP1 via the metallochaperone ZNG1 (ZNG1-METAP1 complex), increasing intracellular SAM production. This promotes PRMT5-mediated symmetrical dimethylarginine (SDMA) methylation of AKT at R391 and R15, facilitating AKT translocation to the plasma membrane, interaction with mTORC2, and AKT activation to support cell proliferation and gut barrier function. Co-immunoprecipitation, SAM metabolite measurement, mass spectrometry for SDMA modification, AKT localization assay, cell proliferation assay Advanced science Medium 40642900
2024 Proteins whose N-termini are processed by MetAP1 (not MetAP2) are unaffected by MetAP2 loss or inhibition in the context of the UBR4-dependent Arg/N-degron pathway, demonstrating substrate specificity partitioning between MetAP1 and MetAP2 for N-degron pathway entry. Reporter assays, CRISPR-Cas9 knockout of MetAP2, bioinformatic analysis of endogenous substrates bioRxivpreprint Medium bio_10.1101_2024.10.03.616566

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proceedings of the National Academy of Sciences of the United States of America 554 9177176
1995 Amino-terminal protein processing in Saccharomyces cerevisiae is an essential function that requires two distinct methionine aminopeptidases. Proceedings of the National Academy of Sciences of the United States of America 251 8618900
1998 Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2. Proceedings of the National Academy of Sciences of the United States of America 208 9860943
2010 Protein N-terminal processing: substrate specificity of Escherichia coli and human methionine aminopeptidases. Biochemistry 167 20521764
1999 Selective inhibition of amino-terminal methionine processing by TNP-470 and ovalicin in endothelial cells. Chemistry & biology 93 10574784
2000 Selective inhibition of endothelial cell proliferation by fumagillin is not due to differential expression of methionine aminopeptidases. Journal of cellular biochemistry 83 10760954
2005 Structural basis for the functional differences between type I and type II human methionine aminopeptidases. Biochemistry 79 16274222
2006 Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression. Proceedings of the National Academy of Sciences of the United States of America 75 17114291
2005 Methionine aminopeptidases type I and type II are essential to control cell proliferation. Journal of cellular biochemistry 60 15962312
2005 Methionine aminopeptidase 2 and cancer. Biochimica et biophysica acta 60 16386852
2002 Yeast methionine aminopeptidase type 1 is ribosome-associated and requires its N-terminal zinc finger domain for normal function in vivo. Journal of cellular biochemistry 55 11968008
2002 The specificity in vivo of two distinct methionine aminopeptidases in Saccharomyces cerevisiae. Archives of biochemistry and biophysics 53 11811952
2023 NAC controls cotranslational N-terminal methionine excision in eukaryotes. Science (New York, N.Y.) 48 37347872
2022 Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase. Cell reports 47 35584675
2004 Small molecule inhibitors of methionine aminopeptidase type 2 (MetAP-2). Angiogenesis 38 15516829
2024 NAC guides a ribosomal multienzyme complex for nascent protein processing. Nature 37 39169182
2016 MetAP1 and MetAP2 drive cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state. Oncotarget 35 27542228
2010 Methionine aminopeptidases as potential targets for treatment of gastrointestinal cancers and other tumours. Current drug targets 31 20583970
2017 The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects. Journal of natural products 29 28185457
2008 Synthesis of barbiturate-based methionine aminopeptidase-1 inhibitors. Bioorganic & medicinal chemistry letters 25 18343108
2003 N-terminal methionine removal and methionine metabolism in Saccharomyces cerevisiae. Journal of cellular biochemistry 22 12874831
2008 Discovery, identification, and characterization of candidate pharmacodynamic markers of methionine aminopeptidase-2 inhibition. Journal of proteome research 20 18828628
2006 Structure of the angiogenesis inhibitor ovalicin bound to its noncognate target, human Type 1 methionine aminopeptidase. Protein science : a publication of the Protein Society 20 16823043
1997 A dominant negative mutation in Saccharomyces cerevisiae methionine aminopeptidase-1 affects catalysis and interferes with the function of methionine aminopeptidase-2. Archives of biochemistry and biophysics 20 9367524
2019 LINC00461 affects the survival of patients with renal cell carcinoma by acting as a competing endogenous RNA for microRNA‑942. Oncology reports 19 31545458
2016 Methionine AminoPeptidase Type-2 Inhibitors Targeting Angiogenesis. Current topics in medicinal chemistry 19 26369821
2014 Redox regulation of methionine aminopeptidase 2 activity. The Journal of biological chemistry 19 24700462
2003 A single amino acid residue defines the difference in ovalicin sensitivity between type I and II methionine aminopeptidases. The Journal of biological chemistry 19 14676204
2012 Substituted oxines inhibit endothelial cell proliferation and angiogenesis. Organic & biomolecular chemistry 18 22391578
2014 Beta-aminoketones as prodrugs for selective irreversible inhibitors of type-1 methionine aminopeptidases. Bioorganic & medicinal chemistry letters 17 25293447
2007 Kinetic and mutational studies of the number of interacting divalent cations required by bacterial and human methionine aminopeptidases. Biochemistry 17 17929833
2020 In Vitro and In Vivo Characterization of Potent Antileishmanial Methionine Aminopeptidase 1 Inhibitors. Antimicrobial agents and chemotherapy 15 32179532
2012 Association of single nucleotide polymorphic sites in candidate genes with aggressiveness and deoxynivalenol production in Fusarium graminearum causing wheat head blight. BMC genetics 15 22409447
2011 S1 pocket fingerprints of human and bacterial methionine aminopeptidases determined using fluorogenic libraries of substrates and phosphorus based inhibitors. Biochimie 15 22085501
2000 cis-fumagillin, a new methionine aminopeptidase (type 2) inhibitor produced by Penicillium sp. F2757. The Journal of antibiotics 13 11079802
2025 Mechanism of cotranslational protein N-myristoylation in human cells. Molecular cell 11 40639378
2013 Pyridinylquinazolines selectively inhibit human methionine aminopeptidase-1 in cells. Journal of medicinal chemistry 11 23634668
2024 Proteome- and Transcriptome-Wide Genetic Analysis Identifies Biological Pathways and Candidate Drug Targets for Preeclampsia. Circulation. Genomic and precision medicine 10 39119725
2022 RNA interference screens discover proteases as synthetic lethal partners of PI3K inhibition in breast cancer cells. Theranostics 10 35673573
2013 Pyridinylpyrimidines selectively inhibit human methionine aminopeptidase-1. Bioorganic & medicinal chemistry 10 23507151
2002 Functional expression of human methionine aminopeptidase type 1 in Saccharomyces cerevisiae. Protein and peptide letters 10 12144506
2025 Zinc Alleviates Gut Barrier Dysfunction by Promoting the Methylation of AKT. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 40642900
2019 MapB Protein is the Essential Methionine Aminopeptidase in Mycobacterium tuberculosis. Cells 8 31035386
2016 Recombinant methionine aminopeptidase protein of Babesia microti: immunobiochemical characterization as a vaccine candidate against human babesiosis. Parasitology research 8 27306898
2023 Discovery of cisplatin-binding proteins by competitive cysteinome profiling. RSC chemical biology 6 37654507
2023 HLA-C*15:02 and epidermal growth factor receptor inhibitor-induced erosive pustular dermatosis of the scalp. Clinical and experimental dermatology 6 37710038
2025 Inhibition of methionine aminopeptidase in C2C12 myoblasts disrupts cell integrity via increasing endoplasmic reticulum stress. Biochimica et biophysica acta. Molecular cell research 4 39814187
2021 Design, synthesis and biological evaluation of substituted 3-amino-N-(thiazol-2-yl)pyrazine-2-carboxamides as inhibitors of mycobacterial methionine aminopeptidase 1. Bioorganic chemistry 4 34826708
2005 Evidence of a dominant negative mutant of yeast methionine aminopeptidase type 2 in Saccharomyces cerevisiae. Journal of cellular biochemistry 4 15547949
2025 Mechanism of cotranslational modification of histones H2A and H4 by MetAP1 and NatD. Science advances 3 41417911
2024 Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia. Circulation research 2 39727051
2024 Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models. Molecular cancer therapeutics 1 37940144
2020 METAP1 mutation is a novel candidate for autosomal recessive intellectual disability. Journal of human genetics 1 32764695
2015 Chemical shift assignments of zinc finger domain of methionine aminopeptidase 1 (MetAP1) from Homo sapiens. Biomolecular NMR assignments 1 25921012
2026 NAA40 and NAC cooperate in co-translational histone acetylation in humans. Nature communications 0 41820326
2025 Mycobacterial Methionine Aminopeptidase Type 1c Moonlights as an Anti-association Factor on the 30S Ribosomal Subunit. Journal of molecular biology 0 40441414
2025 Expression and purification of methionine aminopeptidases and N-terminal acetyltransferases. Methods in enzymology 0 40887154
2024 Unveiling Antibiotic Resistance: Genome Sequencing of Streptomycin-Resistant Erwinia amylovora Isolate. Microorganisms 0 39770697
2023 Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase. International journal of molecular sciences 0 38138972

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