MAP2_PYRFU
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 03-AUG-2022, entry version 156.
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;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01975,
CC ECO:0000269|PubMed:12044150};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01975,
CC ECO:0000269|PubMed:12044150};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01975,
CC ECO:0000269|PubMed:12044150};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01975,
CC 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=5.0 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=2.0 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 EnsemblBacteria; AAL80665; AAL80665; 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 OMA; NEIAAHY; -.
DR OrthoDB; 82853at2157; -.
DR PhylomeDB; P56218; -.
DR BRENDA; 3.4.11.18; 5243.
DR EvolutionaryTrace; P56218; -.
DR Proteomes; UP000001013; Chromosome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0070084; P:protein initiator methionine removal; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd01088; MetAP2; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.90.230.10; -; 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 Pfam; PF00557; Peptidase_M24; 1.
DR PRINTS; PR00599; MAPEPTIDASE.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR TIGRFAMs; TIGR00501; met_pdase_II; 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
