SCMU_MYCTU
ID SCMU_MYCTU Reviewed; 199 AA.
AC P9WIB9; L0T9J1; O07746; Q7D7U7;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Secreted chorismate mutase {ECO:0000303|PubMed:15654876};
DE Short=CM {ECO:0000303|PubMed:15654876};
DE EC=5.4.99.5 {ECO:0000269|PubMed:15654876, ECO:0000269|PubMed:15737998};
DE AltName: Full=*MtCM {ECO:0000303|PubMed:15654876};
DE Flags: Precursor;
GN OrderedLocusNames=Rv1885c;
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 CHORISMATE MUTASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, SUBUNIT, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15654876; DOI=10.1111/j.1742-4658.2004.04478.x;
RA Sasso S., Ramakrishnan C., Gamper M., Hilvert D., Kast P.;
RT "Characterization of the secreted chorismate mutase from the pathogen
RT Mycobacterium tuberculosis.";
RL FEBS J. 272:375-389(2005).
RN [3]
RP FUNCTION AS A CHORISMATE MUTASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15737998; DOI=10.1074/jbc.m413026200;
RA Prakash P., Aruna B., Sardesai A.A., Hasnain S.E.;
RT "Purified recombinant hypothetical protein coded by open reading frame
RT Rv1885c of Mycobacterium tuberculosis exhibits a monofunctional AroQ class
RT of periplasmic chorismate mutase activity.";
RL J. Biol. Chem. 280:19641-19648(2005).
RN [4]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [5]
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 [6] {ECO:0007744|PDB:2FP1, ECO:0007744|PDB:2FP2}
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 34-199 IN COMPLEX WITH SUBSTRATE
RP ANALOGS, SUBUNIT, AND DISULFIDE BOND.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16499927; DOI=10.1016/j.jmb.2006.01.069;
RA Okvist M., Dey R., Sasso S., Grahn E., Kast P., Krengel U.;
RT "1.6 A crystal structure of the secreted chorismate mutase from
RT Mycobacterium tuberculosis: novel fold topology revealed.";
RL J. Mol. Biol. 357:1483-1499(2006).
RN [7] {ECO:0007744|PDB:2AO2}
RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 35-199, SUBUNIT, AND DISULFIDE
RP BOND.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16752890; DOI=10.1021/bi0606445;
RA Qamra R., Prakash P., Aruna B., Hasnain S.E., Mande S.C.;
RT "The 2.15 A crystal structure of Mycobacterium tuberculosis chorismate
RT mutase reveals an unexpected gene duplication and suggests a role in host-
RT pathogen interactions.";
RL Biochemistry 45:6997-7005(2006).
RN [8] {ECO:0007744|PDB:2F6L}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 34-199, MUTAGENESIS OF ARG-49;
RP LYS-60; ASP-69; ARG-72; THR-105; GLU-109 AND ARG-134, SUBUNIT, SUBCELLULAR
RP LOCATION, AND DISULFIDE BOND.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17146044; DOI=10.1128/jb.00441-06;
RA Kim S.K., Reddy S.K., Nelson B.C., Vasquez G.B., Davis A., Howard A.J.,
RA Patterson S., Gilliland G.L., Ladner J.E., Reddy P.T.;
RT "Biochemical and structural characterization of the secreted chorismate
RT mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv: an *AroQ enzyme not
RT regulated by the aromatic amino acids.";
RL J. Bacteriol. 188:8638-8648(2006).
CC -!- FUNCTION: Catalyzes the Claisen rearrangement of chorismate to
CC prephenate. May play some role in the pathogenicity.
CC {ECO:0000269|PubMed:15654876, ECO:0000269|PubMed:15737998}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chorismate = prephenate; Xref=Rhea:RHEA:13897,
CC ChEBI:CHEBI:29748, ChEBI:CHEBI:29934; EC=5.4.99.5;
CC Evidence={ECO:0000269|PubMed:15654876, ECO:0000269|PubMed:15737998};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13898;
CC Evidence={ECO:0000269|PubMed:15654876, ECO:0000269|PubMed:15737998};
CC -!- ACTIVITY REGULATION: Tyrosine, phenylalanine, and tryptophan moderately
CC enhance chorismate mutase activity at low concentrations, but
CC allosterically inhibit the enzyme at higher concentrations.
CC {ECO:0000269|PubMed:15737998}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1200 uM for chorismate (at pH 7.5 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:15737998};
CC KM=180 uM for chorismate (at pH 7.5 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:15654876};
CC KM=500 uM for chorismate (with 27.5 nM of protein at pH 7.5 and 37
CC degrees Celsius) {ECO:0000269|PubMed:17146044};
CC KM=670 uM for chorismate (with 8 nM of protein at pH 7.5 and 37
CC degrees Celsius) {ECO:0000269|PubMed:17146044};
CC Vmax=74 umol/min/mg enzyme (at pH 7.5 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:15737998};
CC Note=kcat is 50 sec(-1) (PubMed:15654876). kcat is 26 sec(-1)
CC (PubMed:15737998). {ECO:0000269|PubMed:15654876,
CC ECO:0000269|PubMed:15737998};
CC pH dependence:
CC Optimum pH is 7.5. The activity is dramatically affected under
CC alkaline conditions (pH 9.5). {ECO:0000269|PubMed:15654876,
CC ECO:0000269|PubMed:15737998};
CC Temperature dependence:
CC Optimum temperature is between 37 to 50 degrees Celsius. An increase
CC in temperature does increase enzyme activity, and complete reversible
CC denaturation of the enzyme occurs at a temperature close to 60
CC degrees Celsius. {ECO:0000269|PubMed:15654876,
CC ECO:0000269|PubMed:15737998};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; prephenate biosynthesis;
CC prephenate from chorismate: step 1/1. {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15654876,
CC ECO:0000269|PubMed:15737998, ECO:0000269|PubMed:16499927,
CC ECO:0000269|PubMed:16752890, ECO:0000269|PubMed:17146044}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15654876,
CC ECO:0000269|PubMed:15737998, ECO:0000269|PubMed:17146044}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- MISCELLANEOUS: In the presence of high concentrations of tyrosine,
CC phenylalanine, and tryptophan, the enzyme is completely protected from
CC proteolytic degradation. {ECO:0000269|PubMed:15737998}.
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DR EMBL; AL123456; CCP44651.1; -; Genomic_DNA.
DR PIR; B70516; B70516.
DR RefSeq; NP_216401.1; NC_000962.3.
DR RefSeq; WP_003899064.1; NZ_NVQJ01000013.1.
DR PDB; 2AO2; X-ray; 2.07 A; A/B/C=35-199.
DR PDB; 2F6L; X-ray; 1.70 A; A/B=34-199.
DR PDB; 2FP1; X-ray; 1.55 A; A/B=34-199.
DR PDB; 2FP2; X-ray; 1.64 A; A/B=34-199.
DR PDBsum; 2AO2; -.
DR PDBsum; 2F6L; -.
DR PDBsum; 2FP1; -.
DR PDBsum; 2FP2; -.
DR AlphaFoldDB; P9WIB9; -.
DR SMR; P9WIB9; -.
DR STRING; 83332.Rv1885c; -.
DR BindingDB; P9WIB9; -.
DR ChEMBL; CHEMBL6066; -.
DR DrugBank; DB08648; 8-Hydroxy-2-oxa-bicyclo[3.3.1]non-6-ene-3,5-dicarboxylic acid.
DR PaxDb; P9WIB9; -.
DR PRIDE; P9WIB9; -.
DR DNASU; 885772; -.
DR GeneID; 45425858; -.
DR GeneID; 885772; -.
DR KEGG; mtu:Rv1885c; -.
DR TubercuList; Rv1885c; -.
DR eggNOG; COG1605; Bacteria.
DR OMA; RSAPDCP; -.
DR PhylomeDB; P9WIB9; -.
DR BRENDA; 5.4.99.5; 3445.
DR SABIO-RK; P9WIB9; -.
DR UniPathway; UPA00120; UER00203.
DR PRO; PR:P9WIB9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IDA:MTBBASE.
DR GO; GO:0004106; F:chorismate mutase activity; IDA:UniProtKB.
DR GO; GO:0046417; P:chorismate metabolic process; IDA:UniProtKB.
DR GO; GO:0009697; P:salicylic acid biosynthetic process; IBA:GO_Central.
DR Gene3D; 1.20.59.10; -; 1.
DR InterPro; IPR036263; Chorismate_II_sf.
DR InterPro; IPR008240; Chorismate_mutase_periplasmic.
DR InterPro; IPR036979; CM_dom_sf.
DR InterPro; IPR002701; CM_II_prokaryot.
DR Pfam; PF01817; CM_2; 1.
DR PIRSF; PIRSF026640; Peripl_chor_mut; 1.
DR SMART; SM00830; CM_2; 1.
DR SUPFAM; SSF48600; SSF48600; 1.
DR TIGRFAMs; TIGR01806; CM_mono2; 1.
DR PROSITE; PS51168; CHORISMATE_MUT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Isomerase; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..33
FT /evidence="ECO:0000269|PubMed:15654876"
FT CHAIN 34..199
FT /note="Secreted chorismate mutase"
FT /id="PRO_0000414906"
FT DOMAIN 34..113
FT /note="Chorismate mutase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00515"
FT BINDING 49
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16499927"
FT BINDING 60
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16499927"
FT BINDING 69
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16499927"
FT BINDING 72..76
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16499927"
FT BINDING 105..109
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16499927"
FT BINDING 134
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16499927"
FT DISULFID 160..193
FT /evidence="ECO:0000269|PubMed:16499927,
FT ECO:0000269|PubMed:16752890, ECO:0000269|PubMed:17146044,
FT ECO:0007744|PDB:2AO2, ECO:0007744|PDB:2F6L,
FT ECO:0007744|PDB:2FP1, ECO:0007744|PDB:2FP2"
FT MUTAGEN 49
FT /note="R->A: Less than 1% of the wild-type enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:17146044"
FT MUTAGEN 60
FT /note="K->A: Less than 1% of the wild-type enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:17146044"
FT MUTAGEN 69
FT /note="D->A: No effect on the enzyme activity."
FT /evidence="ECO:0000269|PubMed:17146044"
FT MUTAGEN 72
FT /note="R->A: Less than 1% of the wild-type enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:17146044"
FT MUTAGEN 105
FT /note="T->A: 20% of the wild-type enzyme activity."
FT /evidence="ECO:0000269|PubMed:17146044"
FT MUTAGEN 109
FT /note="E->A: 10% of the wild-type enzyme activity."
FT /evidence="ECO:0000269|PubMed:17146044"
FT MUTAGEN 109
FT /note="E->Q: 40% of the wild-type enzyme activity at pH 7.5
FT and 27% of the wild-type enzyme activity at pH 4."
FT /evidence="ECO:0000269|PubMed:17146044"
FT MUTAGEN 134
FT /note="R->A: Less than 1% of the wild-type enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:17146044"
FT HELIX 40..51
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 53..63
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 70..86
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 91..118
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 131..150
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 152..155
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 160..174
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 179..188
FT /evidence="ECO:0007829|PDB:2FP1"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:2FP1"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:2AO2"
SQ SEQUENCE 199 AA; 21945 MW; BC5DFB776FC3FA1E CRC64;
MLTRPREIYL ATAVSIGILL SLIAPLGPPL ARADGTSQLA ELVDAAAERL EVADPVAAFK
WRAQLPIEDS GRVEQQLAKL GEDARSQHID PDYVTRVFDD QIRATEAIEY SRFSDWKLNP
ASAPPEPPDL SASRSAIDSL NNRMLSQIWS HWSLLSAPSC AAQLDRAKRD IVRSRHLDSL
YQRALTTATQ SYCQALPPA
