RRAAH_MYCTU
ID RRAAH_MYCTU Reviewed; 157 AA.
AC P9WGY3; L0TFG1; P0A666; P96224;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Putative 4-hydroxy-4-methyl-2-oxoglutarate aldolase;
DE Short=HMG aldolase;
DE EC=4.1.3.17;
DE AltName: Full=Oxaloacetate decarboxylase;
DE Short=OAA decarboxylase;
DE EC=4.1.1.112;
DE AltName: Full=Regulator of ribonuclease activity homolog;
DE AltName: Full=RraA-like protein;
GN Name=rraA; OrderedLocusNames=Rv3853; ORFNames=MTCY01A6.15c;
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 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 [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 (1.9 ANGSTROMS).
RX PubMed=12837779; DOI=10.1128/jb.185.14.4057-4065.2003;
RA Johnston J.M., Arcus V.L., Morton C.J., Parker M.W., Baker E.N.;
RT "Crystal structure of a putative methyltransferase from Mycobacterium
RT tuberculosis: misannotation of a genome clarified by protein structural
RT analysis.";
RL J. Bacteriol. 185:4057-4065(2003).
CC -!- FUNCTION: Catalyzes the aldol cleavage of 4-hydroxy-4-methyl-2-
CC oxoglutarate (HMG) into 2 molecules of pyruvate. Also contains a
CC secondary oxaloacetate (OAA) decarboxylase activity due to the common
CC pyruvate enolate transition state formed following C-C bond cleavage in
CC the retro-aldol and decarboxylation reactions (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxy-4-methyl-2-oxoglutarate = 2 pyruvate;
CC Xref=Rhea:RHEA:22748, ChEBI:CHEBI:15361, ChEBI:CHEBI:58276;
CC EC=4.1.3.17;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxaloacetate = CO2 + pyruvate; Xref=Rhea:RHEA:15641,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:16526; EC=4.1.1.112;
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250};
CC Note=Divalent metal cation. {ECO:0000250};
CC -!- SUBUNIT: Homotrimer. {ECO:0000250}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the class II aldolase/RraA-like family.
CC {ECO:0000305}.
CC -!- CAUTION: Originally described as a SAM-dependent methyltransferase
CC (PubMed:9634230), the crystal structure does not resemble other known
CC SAM-dependent methyltransferases. The structure does resemble the
CC phosphohistidine domain of several phosphotransfer system proteins. The
CC protein does not bind S-adenosylmethionine cofactor or potential
CC methyltransferase substrate molecules. {ECO:0000305|PubMed:9634230}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL123456; CCP46682.1; -; Genomic_DNA.
DR PIR; B70655; B70655.
DR RefSeq; NP_218370.1; NC_000962.3.
DR RefSeq; WP_003399786.1; NZ_NVQJ01000057.1.
DR PDB; 1NXJ; X-ray; 1.90 A; A/B/C=2-157.
DR PDBsum; 1NXJ; -.
DR AlphaFoldDB; P9WGY3; -.
DR SMR; P9WGY3; -.
DR STRING; 83332.Rv3853; -.
DR DrugBank; DB04343; Glyoxylic acid.
DR PaxDb; P9WGY3; -.
DR GeneID; 45427857; -.
DR GeneID; 886181; -.
DR KEGG; mtu:Rv3853; -.
DR TubercuList; Rv3853; -.
DR eggNOG; COG0684; Bacteria.
DR OMA; RSCDTQF; -.
DR PhylomeDB; P9WGY3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0047443; F:4-hydroxy-4-methyl-2-oxoglutarate aldolase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008948; F:oxaloacetate decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0008428; F:ribonuclease inhibitor activity; IEA:InterPro.
DR GO; GO:0051252; P:regulation of RNA metabolic process; IEA:InterPro.
DR CDD; cd16841; RraA_family; 1.
DR InterPro; IPR010203; RraA.
DR InterPro; IPR005493; RraA/RraA-like.
DR InterPro; IPR036704; RraA/RraA-like_sf.
DR Pfam; PF03737; RraA-like; 1.
DR SUPFAM; SSF89562; SSF89562; 1.
DR TIGRFAMs; TIGR01935; NOT-MenG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Lyase; Metal-binding; Reference proteome.
FT CHAIN 1..157
FT /note="Putative 4-hydroxy-4-methyl-2-oxoglutarate aldolase"
FT /id="PRO_0000209623"
FT BINDING 78..81
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 101
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT HELIX 8..15
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 35..43
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:1NXJ"
FT HELIX 49..56
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:1NXJ"
FT HELIX 79..87
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 92..100
FT /evidence="ECO:0007829|PDB:1NXJ"
FT HELIX 102..105
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 108..117
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 145..149
FT /evidence="ECO:0007829|PDB:1NXJ"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:1NXJ"
SQ SEQUENCE 157 AA; 16235 MW; 92BD93F60B66E793 CRC64;
MAISFRPTAD LVDDIGPDVR SCDLQFRQFG GRSQFAGPIS TVRCFQDNAL LKSVLSQPSA
GGVLVIDGAG SLHTALVGDV IAELARSTGW TGLIVHGAVR DAAALRGIDI GIKALGTNPR
KSTKTGAGER DVEITLGGVT FVPGDIAYSD DDGIIVV
