Secreted chorismate mutase precursor - Mycobacterium tuberculosis

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O07746 (SCMU_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 92. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Secreted chorismate mutase
Short name=*MtCM
Short name=CM
EC=5.4.99.5

Gene names

Ordered Locus Names:

Rv1885c, MT1933

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	199 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the Claisen rearrangement of chorismate to prephenate. May play some role in the pathogenicity. Ref.3 Ref.4
Catalytic activity	Chorismate = prephenate.
Enzyme regulation	Tyrosine, phenylalanine, and tryptophan moderately enhance chorismate mutase activity at low concentrations, but allosterically inhibit the enzyme at higher concentrations. Ref.4
Pathway	Metabolic intermediate biosynthesis; prephenate biosynthesis; prephenate from chorismate: step 1/1.
Subunit structure	Homodimer. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Secreted Ref.3 Ref.4 Ref.7.
Miscellaneous	Was identified as a high-confidence drug target (Ref.8). In the presence of high concentrations of tyrosine, phenylalanine, and tryptophan, the enzyme is completely protected from proteolytic degradation.
Sequence similarities	Contains 1 chorismate mutase domain.
Biophysicochemical properties	Kinetic parameters: K_M=120 µM for chorismate (at pH 7.5 and at 37 degrees Celsius, Ref.4) Ref.3 Ref.4 K_M=180 µM for chorismate (at pH 7.5 and at 30 degrees Celsius, Ref.3) K_M=500 µM for chorismate (with 27.5 nM of protein at pH 7.5 and at 37 degrees Celsius, Ref.7) K_M=670 µM for chorismate (with 8 nM of protein at pH 7.5 and at 37 degrees Celsius, Ref.7) V_max=74 µmol/min/mg enzyme (at pH 7.5 and at 37 degrees Celsius, Ref.4) pH dependence: Optimum pH is 7.5. The activity is dramatically affected under alkaline conditions (pH 9.5). Temperature dependence: Optimum temperature is between 37 to 50 degrees Celsius. An increase in temperature does increase enzyme activity, and complete reversible denaturation of the enzyme occurs at a temperature close to 60 degrees Celsius.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Isomerase
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chorismate metabolic process Inferred from direct assay Ref.3. Source: UniProtKB
Cellular_component	extracellular region Inferred from direct assay PubMed 15654875 Ref.7. Source: MTBBASE
Molecular_function	chorismate mutase activity Inferred from direct assay Ref.3. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 33

Chain

34 – 199

166

Secreted chorismate mutase

PRO_0000414906

Regions

Domain

34 – 113

Chorismate mutase

Region

72 – 76

Substrate binding

Region

105 – 109

Substrate binding

Sites

Binding site

Substrate

Binding site

Substrate

Binding site

Substrate

Binding site

Substrate

Binding site

134

Substrate

Amino acid modifications

Disulfide bond

160 ↔ 193

Experimental info

Mutagenesis

R → A: Less than 1% of the wild-type enzyme activity. Ref.7

Mutagenesis

K → A: Less than 1% of the wild-type enzyme activity. Ref.7

Mutagenesis

D → A: No effect on the enzyme activity. Ref.7

Mutagenesis

R → A: Less than 1% of the wild-type enzyme activity. Ref.7

Mutagenesis

105

T → A: 20% of the wild-type enzyme activity. Ref.7

Mutagenesis

109

E → A: 10% of the wild-type enzyme activity. Ref.7

Mutagenesis

109

E → Q: 40% of the wild-type enzyme activity at pH 7.5 and 27% of the wild-type enzyme activity at pH 4. Ref.7

Mutagenesis

134

R → A: Less than 1% of the wild-type enzyme activity. Ref.7

Secondary structure

199

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

O07746 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: BC5DFB776FC3FA1E
Show »

FASTA

199

21,945

        10         20         30         40         50         60 
MLTRPREIYL ATAVSIGILL SLIAPLGPPL ARADGTSQLA ELVDAAAERL EVADPVAAFK 

        70         80         90        100        110        120 
WRAQLPIEDS GRVEQQLAKL GEDARSQHID PDYVTRVFDD QIRATEAIEY SRFSDWKLNP 

       130        140        150        160        170        180 
ASAPPEPPDL SASRSAIDSL NNRMLSQIWS HWSLLSAPSC AAQLDRAKRD IVRSRHLDSL 

       190 
YQRALTTATQ SYCQALPPA

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Characterization of the secreted chorismate mutase from the pathogen Mycobacterium tuberculosis." Sasso S., Ramakrishnan C., Gamper M., Hilvert D., Kast P. FEBS J. 272:375-389(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A CHORISMATE MUTASE, MASS SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, SUBUNIT. Strain: ATCC 25618 / H37Rv.
[4]	"Purified recombinant hypothetical protein coded by open reading frame Rv1885c of Mycobacterium tuberculosis exhibits a monofunctional AroQ class of periplasmic chorismate mutase activity." Prakash P., Aruna B., Sardesai A.A., Hasnain S.E. J. Biol. Chem. 280:19641-19648(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A CHORISMATE MUTASE, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBCELLULAR LOCATION, SUBUNIT. Strain: ATCC 25618 / H37Rv.
[5]	"1.6 A crystal structure of the secreted chorismate mutase from Mycobacterium tuberculosis: novel fold topology revealed." Okvist M., Dey R., Sasso S., Grahn E., Kast P., Krengel U. J. Mol. Biol. 357:1483-1499(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 34-199 IN COMPLEX WITH SUBSTRATE ANALOGS, SUBUNIT. Strain: ATCC 25618 / H37Rv.
[6]	"The 2.15 A crystal structure of Mycobacterium tuberculosis chorismate mutase reveals an unexpected gene duplication and suggests a role in host-pathogen interactions." Qamra R., Prakash P., Aruna B., Hasnain S.E., Mande S.C. Biochemistry 45:6997-7005(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 35-199, SUBUNIT. Strain: ATCC 25618 / H37Rv.
[7]	*"Biochemical and structural characterization of the secreted chorismate mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv: an AroQ enzyme not regulated by the aromatic amino acids."** Kim S.K., Reddy S.K., Nelson B.C., Vasquez G.B., Davis A., Howard A.J., Patterson S., Gilliland G.L., Ladner J.E., Reddy P.T. J. Bacteriol. 188:8638-8648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 34-199, MUTAGENESIS OF ARG-49; LYS-60; ASP-69; ARG-72; THR-105; GLU-109 AND ARG-134, SUBUNIT, SUBCELLULAR LOCATION. Strain: ATCC 25618 / H37Rv.
[8]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AE000516 Genomic DNA. Translation: AAK46206.1.
BX842578 Genomic DNA. Translation: CAB10064.1.
AL123456 Genomic DNA. Translation: CCP44651.1.

PIR

B70516.

RefSeq

NP_216401.1. NC_000962.3.
NP_336392.1. NC_002755.2.
YP_006515285.1. NC_018143.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AO2	X-ray	2.07	A/B/C	35-199	[»]
2F6L	X-ray	1.70	A/B	34-199	[»]
2FP1	X-ray	1.55	A/B	34-199	[»]
2FP2	X-ray	1.64	A/B	34-199	[»]

ProteinModelPortal

O07746.

SMR

O07746. Positions 35-199.

ModBase

Search...

Protein-protein interaction databases

STRING

83332.Rv1885c.

Proteomic databases

PRIDE

O07746.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK46206; AAK46206; MT1933.

GeneID

13316676.
885772.
923642.

KEGG

mtc:MT1933.
mtu:Rv1885c.
mtv:RVBD_1885c.

PATRIC

18126016. VBIMycTub22151_2120.

Organism-specific databases

TubercuList

Rv1885c.

Phylogenomic databases

HOGENOM

HOG000257623.

K04093.

OMA

QDSPREE.

ProtClustDB

PRK09269.

Enzyme and pathway databases

UniPathway

UPA00120; UER00203.

Family and domain databases

Gene3D

1.20.59.10. 1 hit.

InterPro

IPR002701. Chorismate_mutase.
IPR008240. Chorismate_mutase_periplasmic.
IPR020822. Chorismate_mutase_type_II.
[Graphical view]

Pfam

PF01817. CM_2. 1 hit.
[Graphical view]

PIRSF

PIRSF026640. Peripl_chor_mut. 1 hit.

SMART

SM00830. CM_2. 1 hit.
[Graphical view]

SUPFAM

SSF48600. Chorismate_mut. 1 hit.

TIGRFAMs

TIGR01806. CM_mono2. 1 hit.

PROSITE

PS51168. CHORISMATE_MUT_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O07746.

ChEMBL

CHEMBL6066.

EvolutionaryTrace

O07746.

Entry information

Entry name

SCMU_MYCTU

Accession

Primary (citable) accession number: O07746
Secondary accession number(s): L0T9J1, Q7D7U7

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 25, 2012
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Other

Entry information

Relevant documents