ID   MAP2_PYRFU              Reviewed;         295 AA.
AC   P56218;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 1.
DT   27-MAR-2024, entry version 162.
DE   RecName: Full=Methionine aminopeptidase {ECO:0000255|HAMAP-Rule:MF_01975};
DE            Short=MAP {ECO:0000255|HAMAP-Rule:MF_01975};
DE            Short=MetAP {ECO:0000255|HAMAP-Rule:MF_01975};
DE            EC=3.4.11.18 {ECO:0000255|HAMAP-Rule:MF_01975};
DE   AltName: Full=Peptidase M {ECO:0000255|HAMAP-Rule:MF_01975};
GN   Name=map {ECO:0000255|HAMAP-Rule:MF_01975}; OrderedLocusNames=PF0541;
OS   Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1).
OC   Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC   Pyrococcus.
OX   NCBI_TaxID=186497;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX   PubMed=10430560; DOI=10.1093/genetics/152.4.1299;
RA   Maeder D.L., Weiss R.B., Dunn D.M., Cherry J.L., Gonzalez J.M.,
RA   DiRuggiero J., Robb F.T.;
RT   "Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P.
RT   horikoshii inferred from complete genomic sequences.";
RL   Genetics 152:1299-1305(1999).
RN   [2]
RP   PROTEIN SEQUENCE OF 1-35, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, AND MASS SPECTROMETRY.
RC   STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX   PubMed=9399590; DOI=10.1093/oxfordjournals.jbchem.a021831;
RA   Tsunasawa S., Izu Y., Miyagi M., Kato I.;
RT   "Methionine aminopeptidase from the hyperthermophilic Archaeon Pyrococcus
RT   furiosus: molecular cloning and overexpression in Escherichia coli of the
RT   gene, and characteristics of the enzyme.";
RL   J. Biochem. 122:843-850(1997).
RN   [3]
RP   COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=12044150; DOI=10.1021/bi020138p;
RA   Meng L., Ruebush S., D'souza V.M., Copik A.J., Tsunasawa S., Holz R.C.;
RT   "Overexpression and divalent metal binding properties of the methionyl
RT   aminopeptidase from Pyrococcus furiosus.";
RL   Biochemistry 41:7199-7208(2002).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH COBALT, AND
RP   MUTAGENESIS OF HIS-161 AND HIS-173.
RX   PubMed=9811545; DOI=10.1006/jmbi.1998.2146;
RA   Tahirov T.H., Oki H., Tsukihara T., Ogasahara K., Yutani K., Ogata K.,
RA   Izu Y., Tsunasawa S., Kato I.;
RT   "Crystal structure of methionine aminopeptidase from hyperthermophile,
RT   Pyrococcus furiosus.";
RL   J. Mol. Biol. 284:101-124(1998).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH MANGANESE AND
RP   METHIONINE.
RX   PubMed=15628852; DOI=10.1021/bi048123+;
RA   Copik A.J., Nocek B.P., Swierczek S.I., Ruebush S., Jang S.B., Meng L.,
RA   D'souza V.M., Peters J.W., Bennett B., Holz R.C.;
RT   "EPR and X-ray crystallographic characterization of the product-bound form
RT   of the MnII-loaded methionyl aminopeptidase from Pyrococcus furiosus.";
RL   Biochemistry 44:121-129(2005).
CC   -!- FUNCTION: Removes the N-terminal methionine from nascent proteins. The
CC       N-terminal methionine is often cleaved when the second residue in the
CC       primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser,
CC       Thr, or Val). {ECO:0000255|HAMAP-Rule:MF_01975,
CC       ECO:0000269|PubMed:9399590}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of N-terminal amino acids, preferentially methionine,
CC         from peptides and arylamides.; EC=3.4.11.18;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01975,
CC         ECO:0000269|PubMed:9399590};
CC   -!- COFACTOR:
CC       Name=Co(2+); Xref=ChEBI:CHEBI:48828; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_01975, ECO:0000269|PubMed:12044150};
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_01975, ECO:0000269|PubMed:12044150};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_01975, ECO:0000269|PubMed:12044150};
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_01975, ECO:0000269|PubMed:12044150};
CC       Note=Binds 2 divalent metal cations per subunit. Has a high-affinity
CC       and a low affinity metal-binding site. The true nature of the
CC       physiological cofactor is under debate. The enzyme is active with
CC       cobalt, zinc, manganese or divalent iron ions. Most likely, methionine
CC       aminopeptidases function as mononuclear Fe(2+)-metalloproteases under
CC       physiological conditions, and the catalytically relevant metal-binding
CC       site has been assigned to the histidine-containing high-affinity site.
CC       {ECO:0000255|HAMAP-Rule:MF_01975, ECO:0000269|PubMed:12044150};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=9.2 mM for a Met-Ala-Ser peptide (for the Fe(2+)-complexed enzyme)
CC         {ECO:0000269|PubMed:12044150, ECO:0000269|PubMed:9399590};
CC         KM=11.8 mM for a Met-Ala-Ser peptide (for the Co(2+)-complexed
CC         enzyme) {ECO:0000269|PubMed:12044150, ECO:0000269|PubMed:9399590};
CC         KM=5 mM for a Met-Gly-Met-Met peptide (for the Fe(2+)-complexed
CC         enzyme) {ECO:0000269|PubMed:12044150, ECO:0000269|PubMed:9399590};
CC         KM=5.1 mM for a Met-Gly-Met-Met peptide (for the Co(2+)-complexed
CC         enzyme) {ECO:0000269|PubMed:12044150, ECO:0000269|PubMed:9399590};
CC         KM=1.3 mM for a Met-Ser-Ser-His-Arg-Trp-Asp-Trp peptide (for the
CC         Fe(2+)-complexed enzyme) {ECO:0000269|PubMed:12044150,
CC         ECO:0000269|PubMed:9399590};
CC         KM=2 mM for a Met-Ser-Ser-His-Arg-Trp-Asp-Trp peptide (for the
CC         Co(2+)-complexed enzyme) {ECO:0000269|PubMed:12044150,
CC         ECO:0000269|PubMed:9399590};
CC       pH dependence:
CC         Optimum pH is 7-8. {ECO:0000269|PubMed:12044150,
CC         ECO:0000269|PubMed:9399590};
CC       Temperature dependence:
CC         Optimum temperature is about 90 degrees Celsius.
CC         {ECO:0000269|PubMed:12044150, ECO:0000269|PubMed:9399590};
CC   -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_01975,
CC       ECO:0000269|PubMed:15628852, ECO:0000269|PubMed:9811545}.
CC   -!- MASS SPECTROMETRY: Mass=32848; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:9399590};
CC   -!- SIMILARITY: Belongs to the peptidase M24A family. Methionine
CC       aminopeptidase archaeal type 2 subfamily. {ECO:0000255|HAMAP-
CC       Rule:MF_01975}.
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DR   EMBL; AE009950; AAL80665.1; -; Genomic_DNA.
DR   PIR; JC5671; JC5671.
DR   RefSeq; WP_011011659.1; NZ_CP023154.1.
DR   PDB; 1WKM; X-ray; 2.30 A; A/B=1-295.
DR   PDB; 1XGM; X-ray; 2.80 A; A/B=1-295.
DR   PDB; 1XGN; X-ray; 2.90 A; A/B=1-295.
DR   PDB; 1XGO; X-ray; 3.50 A; A=1-295.
DR   PDB; 1XGS; X-ray; 1.75 A; A/B=1-295.
DR   PDB; 2DFI; X-ray; 2.10 A; A/B=1-292.
DR   PDB; 6LVH; X-ray; 3.20 A; A=1-295.
DR   PDB; 6M00; X-ray; 3.20 A; A=1-295.
DR   PDBsum; 1WKM; -.
DR   PDBsum; 1XGM; -.
DR   PDBsum; 1XGN; -.
DR   PDBsum; 1XGO; -.
DR   PDBsum; 1XGS; -.
DR   PDBsum; 2DFI; -.
DR   PDBsum; 6LVH; -.
DR   PDBsum; 6M00; -.
DR   AlphaFoldDB; P56218; -.
DR   SMR; P56218; -.
DR   STRING; 186497.PF0541; -.
DR   ChEMBL; CHEMBL4857; -.
DR   MEROPS; M24.035; -.
DR   PaxDb; 186497-PF0541; -.
DR   GeneID; 41712345; -.
DR   KEGG; pfu:PF0541; -.
DR   PATRIC; fig|186497.12.peg.569; -.
DR   eggNOG; arCOG01001; Archaea.
DR   HOGENOM; CLU_015857_7_0_2; -.
DR   OrthoDB; 372008at2157; -.
DR   PhylomeDB; P56218; -.
DR   BRENDA; 3.4.11.18; 5243.
DR   EvolutionaryTrace; P56218; -.
DR   Proteomes; UP000001013; Chromosome.
DR   GO; GO:0004239; F:initiator methionyl aminopeptidase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd01088; MetAP2; 1.
DR   Gene3D; 3.90.230.10; Creatinase/methionine aminopeptidase superfamily; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   HAMAP; MF_01975; MetAP_2_arc; 1.
DR   InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR   InterPro; IPR028595; MetAP_archaeal.
DR   InterPro; IPR000994; Pept_M24.
DR   InterPro; IPR001714; Pept_M24_MAP.
DR   InterPro; IPR002468; Pept_M24A_MAP2.
DR   InterPro; IPR018349; Pept_M24A_MAP2_BS.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   NCBIfam; TIGR00501; met_pdase_II; 1.
DR   PANTHER; PTHR45777; METHIONINE AMINOPEPTIDASE 2; 1.
DR   PANTHER; PTHR45777:SF2; METHIONINE AMINOPEPTIDASE 2; 1.
DR   Pfam; PF00557; Peptidase_M24; 1.
DR   PRINTS; PR00599; MAPEPTIDASE.
DR   SUPFAM; SSF55920; Creatinase/aminopeptidase; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS01202; MAP_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Aminopeptidase; Direct protein sequencing; Hydrolase;
KW   Metal-binding; Protease; Reference proteome.
FT   CHAIN           1..295
FT                   /note="Methionine aminopeptidase"
FT                   /id="PRO_0000148978"
FT   BINDING         62
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01975"
FT   BINDING         82
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT   BINDING         93
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT   BINDING         93
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT   BINDING         153
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT   BINDING         161
FT                   /ligand="substrate"
FT   BINDING         187
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT   BINDING         280
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT   BINDING         280
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT   MUTAGEN         161
FT                   /note="H->A: Reduces enzymatic activity by 96% at 37
FT                   degrees Celsius and by 88% at 87 degrees Celsius; when
FT                   associated with A-173."
FT                   /evidence="ECO:0000269|PubMed:9811545"
FT   MUTAGEN         173
FT                   /note="H->A: Reduces enzymatic activity by 96% at 37
FT                   degrees Celsius and by 88% at 87 degrees Celsius; when
FT                   associated with A-161."
FT                   /evidence="ECO:0000269|PubMed:9811545"
FT   HELIX           3..23
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   HELIX           30..43
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          47..50
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          53..56
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          59..61
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          78..87
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          90..99
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   HELIX           106..121
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   HELIX           129..140
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   TURN            141..143
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          148..150
FT                   /evidence="ECO:0007829|PDB:1XGM"
FT   STRAND          152..154
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          159..161
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          165..169
FT                   /evidence="ECO:0007829|PDB:1XGN"
FT   STRAND          183..186
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          189..193
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          197..208
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   HELIX           217..229
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   TURN            230..232
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          235..237
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   HELIX           238..240
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   TURN            241..243
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   HELIX           246..258
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          261..270
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          276..278
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          280..285
FT                   /evidence="ECO:0007829|PDB:1XGS"
FT   STRAND          287..292
FT                   /evidence="ECO:0007829|PDB:1XGS"
SQ   SEQUENCE   295 AA;  32842 MW;  9739BC55F812E65B CRC64;
     MDTEKLMKAG EIAKKVREKA IKLARPGMLL LELAESIEKM IMELGGKPAF PVNLSINEIA
     AHYTPYKGDT TVLKEGDYLK IDVGVHIDGF IADTAVTVRV GMEEDELMEA AKEALNAAIS
     VARAGVEIKE LGKAIENEIR KRGFKPIVNL SGHKIERYKL HAGISIPNIY RPHDNYVLKE
     GDVFAIEPFA TIGAGQVIEV PPTLIYMYVR DVPVRVAQAR FLLAKIKREY GTLPFAYRWL
     QNDMPEGQLK LALKTLEKAG AIYGYPVLKE IRNGIVAQFE HTIIVEKDSV IVTTE
//