MAP12_MYCTU
ID MAP12_MYCTU Reviewed; 285 AA.
AC P9WK19; L0TDS5; O33343; P0A5J2;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Methionine aminopeptidase 2 {ECO:0000255|HAMAP-Rule:MF_01974};
DE Short=MAP 2 {ECO:0000255|HAMAP-Rule:MF_01974};
DE Short=MetAP 2 {ECO:0000255|HAMAP-Rule:MF_01974};
DE EC=3.4.11.18 {ECO:0000255|HAMAP-Rule:MF_01974};
DE AltName: Full=Peptidase M {ECO:0000255|HAMAP-Rule:MF_01974};
GN Name=map {ECO:0000255|HAMAP-Rule:MF_01974}; Synonyms=mapB;
GN OrderedLocusNames=Rv2861c; ORFNames=MTV003.07c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION AS A METHIONINE AMINOPEPTIDASE, SUBSTRATE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND MASS SPECTROMETRY.
RX PubMed=19688379; DOI=10.1007/s00284-009-9470-3;
RA Zhang X., Chen S., Hu Z., Zhang L., Wang H.;
RT "Expression and characterization of two functional methionine
RT aminopeptidases from Mycobacterium tuberculosis H37Rv.";
RL Curr. Microbiol. 59:520-525(2009).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) IN COMPLEXES WITH COBALT IONS AND
RP METHIONINE.
RX PubMed=15882055; DOI=10.1021/bi0501176;
RA Addlagatta A., Quillin M.L., Omotoso O., Liu J.O., Matthews B.W.;
RT "Identification of an SH3-binding motif in a new class of methionine
RT aminopeptidases from Mycobacterium tuberculosis suggests a mode of
RT interaction with the ribosome.";
RL Biochemistry 44:7166-7174(2005).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS AND
RP DIVALENT CATIONS, FUNCTION AS A METHIONINE AMINOPEPTIDASE,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND COFACTOR.
RX PubMed=20038112; DOI=10.1021/jm901624n;
RA Lu J.P., Chai S.C., Ye Q.Z.;
RT "Catalysis and inhibition of Mycobacterium tuberculosis methionine
RT aminopeptidase.";
RL J. Med. Chem. 53:1329-1337(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS
RP AND MANGANESE IONS, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=21465667; DOI=10.1002/cmdc.201100003;
RA Lu J.P., Yuan X.H., Yuan H., Wang W.L., Wan B., Franzblau S.G., Ye Q.Z.;
RT "Inhibition of Mycobacterium tuberculosis methionine aminopeptidases by
RT bengamide derivatives.";
RL ChemMedChem 6:1041-1048(2011).
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). Requires deformylation of the N(alpha)-formylated
CC initiator methionine before it can be hydrolyzed. {ECO:0000255|HAMAP-
CC Rule:MF_01974, ECO:0000269|PubMed:19688379,
CC ECO:0000269|PubMed:20038112}.
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_01974};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01974,
CC ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01974};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01974,
CC ECO:0000269|PubMed:20038112, ECO:0000269|PubMed:21465667};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01974,
CC ECO:0000269|PubMed:20038112};
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_01974, ECO:0000305|PubMed:20038112};
CC -!- ACTIVITY REGULATION: Inhibited by bengamide derivatives and by various
CC metalloform-selective inhibitors. {ECO:0000269|PubMed:20038112,
CC ECO:0000269|PubMed:21465667}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=58 uM for Met-Gly-Met-Met (at pH 7.5 and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:19688379, ECO:0000269|PubMed:20038112};
CC KM=394 uM for Met-Ala-Ser (at pH 7.5 and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:19688379, ECO:0000269|PubMed:20038112};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius. It lost all its activities
CC at 55 degrees Celsius. {ECO:0000269|PubMed:19688379,
CC ECO:0000269|PubMed:20038112};
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_01974}.
CC -!- MASS SPECTROMETRY: Mass=32516; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:19688379};
CC -!- SIMILARITY: Belongs to the peptidase M24A family. Methionine
CC aminopeptidase type 1 subfamily. {ECO:0000255|HAMAP-Rule:MF_01974}.
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DR EMBL; AL123456; CCP45662.1; -; Genomic_DNA.
DR PIR; G70885; G70885.
DR RefSeq; WP_003899513.1; NZ_NVQJ01000006.1.
DR RefSeq; YP_177911.1; NC_000962.3.
DR PDB; 1Y1N; X-ray; 1.51 A; A=1-285.
DR PDB; 1YJ3; X-ray; 1.60 A; A=1-285.
DR PDB; 3IU7; X-ray; 1.40 A; A=1-285.
DR PDB; 3IU8; X-ray; 1.85 A; A=1-285.
DR PDB; 3IU9; X-ray; 1.75 A; A=1-285.
DR PDB; 3PKA; X-ray; 1.25 A; A=1-285.
DR PDB; 3PKB; X-ray; 1.25 A; A=1-285.
DR PDB; 3PKC; X-ray; 1.47 A; A=1-285.
DR PDB; 3PKD; X-ray; 1.47 A; A=1-285.
DR PDB; 3PKE; X-ray; 1.60 A; A=1-285.
DR PDB; 3ROR; X-ray; 2.00 A; A=1-285.
DR PDB; 4IDY; X-ray; 2.00 A; A=1-285.
DR PDB; 4IEC; X-ray; 2.00 A; A=1-285.
DR PDB; 4IF7; X-ray; 2.00 A; A=1-285.
DR PDB; 4OOK; X-ray; 1.90 A; A=1-283.
DR PDBsum; 1Y1N; -.
DR PDBsum; 1YJ3; -.
DR PDBsum; 3IU7; -.
DR PDBsum; 3IU8; -.
DR PDBsum; 3IU9; -.
DR PDBsum; 3PKA; -.
DR PDBsum; 3PKB; -.
DR PDBsum; 3PKC; -.
DR PDBsum; 3PKD; -.
DR PDBsum; 3PKE; -.
DR PDBsum; 3ROR; -.
DR PDBsum; 4IDY; -.
DR PDBsum; 4IEC; -.
DR PDBsum; 4IF7; -.
DR PDBsum; 4OOK; -.
DR AlphaFoldDB; P9WK19; -.
DR SMR; P9WK19; -.
DR STRING; 83332.Rv2861c; -.
DR DrugBank; DB02909; 5-(2-Chlorophenyl)Furan-2-Carboxylic Acid.
DR MEROPS; M24.A06; -.
DR PaxDb; P9WK19; -.
DR DNASU; 888596; -.
DR GeneID; 45426848; -.
DR GeneID; 888596; -.
DR KEGG; mtu:Rv2861c; -.
DR TubercuList; Rv2861c; -.
DR eggNOG; COG0024; Bacteria.
DR OMA; GDHAYTF; -.
DR PhylomeDB; P9WK19; -.
DR BRENDA; 3.4.11.18; 3445.
DR PRO; PR:P9WK19; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0050897; F:cobalt ion binding; IDA:MTBBASE.
DR GO; GO:0005506; F:iron ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:MTBBASE.
DR GO; GO:0016151; F:nickel cation binding; IDA:MTBBASE.
DR GO; GO:0006555; P:methionine metabolic process; IDA:MTBBASE.
DR GO; GO:0070084; P:protein initiator methionine removal; IBA:GO_Central.
DR GO; GO:0035551; P:protein initiator methionine removal involved in protein maturation; IDA:MTBBASE.
DR CDD; cd01086; MetAP1; 1.
DR Gene3D; 3.90.230.10; -; 1.
DR HAMAP; MF_01974; MetAP_1; 1.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR001714; Pept_M24_MAP.
DR InterPro; IPR002467; Pept_M24A_MAP1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR PRINTS; PR00599; MAPEPTIDASE.
DR SUPFAM; SSF55920; SSF55920; 1.
DR TIGRFAMs; TIGR00500; met_pdase_I; 1.
DR PROSITE; PS00680; MAP_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminopeptidase; Hydrolase; Metal-binding; Protease;
KW Reference proteome.
FT CHAIN 1..285
FT /note="Methionine aminopeptidase 2"
FT /id="PRO_0000148948"
FT BINDING 114
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT BINDING 131
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT BINDING 142
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT BINDING 142
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT BINDING 205
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT BINDING 212
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT BINDING 238
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT BINDING 269
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT BINDING 269
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01974,
FT ECO:0000269|PubMed:15882055, ECO:0000269|PubMed:20038112,
FT ECO:0000269|PubMed:21465667"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:3IU7"
FT HELIX 44..66
FT /evidence="ECO:0007829|PDB:3PKA"
FT HELIX 74..87
FT /evidence="ECO:0007829|PDB:3PKA"
FT TURN 93..96
FT /evidence="ECO:0007829|PDB:3PKA"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 127..136
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 139..148
FT /evidence="ECO:0007829|PDB:3PKA"
FT HELIX 154..172
FT /evidence="ECO:0007829|PDB:3PKA"
FT HELIX 182..192
FT /evidence="ECO:0007829|PDB:3PKA"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:3PKB"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 233..237
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 240..244
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 269..274
FT /evidence="ECO:0007829|PDB:3PKA"
FT STRAND 276..283
FT /evidence="ECO:0007829|PDB:3PKA"
SQ SEQUENCE 285 AA; 30891 MW; E69831250E6C6130 CRC64;
MPSRTALSPG VLSPTRPVPN WIARPEYVGK PAAQEGSEPW VQTPEVIEKM RVAGRIAAGA
LAEAGKAVAP GVTTDELDRI AHEYLVDNGA YPSTLGYKGF PKSCCTSLNE VICHGIPDST
VITDGDIVNI DVTAYIGGVH GDTNATFPAG DVADEHRLLV DRTREATMRA INTVKPGRAL
SVIGRVIESY ANRFGYNVVR DFTGHGIGTT FHNGLVVLHY DQPAVETIMQ PGMTFTIEPM
INLGALDYEI WDDGWTVVTK DRKWTAQFEH TLLVTDTGVE ILTCL
