KDC_MYCTU
ID KDC_MYCTU Reviewed; 560 AA.
AC P9WG37; L0T537; O53865; Q7D958;
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=Alpha-keto-acid decarboxylase;
DE Short=KDC;
DE EC=4.1.1.-;
GN Name=kdc; OrderedLocusNames=Rv0853c;
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 SEQUENCE REVISION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12368430; DOI=10.1099/00221287-148-10-2967;
RA Camus J.-C., Pryor M.J., Medigue C., Cole S.T.;
RT "Re-annotation of the genome sequence of Mycobacterium tuberculosis
RT H37Rv.";
RL Microbiology 148:2967-2973(2002).
RN [3]
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 [4]
RP FUNCTION AS AN ALPHA-KETO-ACID DECARBOXYLASE, AND REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18086676; DOI=10.1074/jbc.m706569200;
RA Werther T., Spinka M., Tittmann K., Schuetz A., Golbik R.,
RA Mrestani-Klaus C., Huebner G., Koenig S.;
RT "Amino acids allosterically regulate the thiamine diphosphate-dependent
RT alpha-keto acid decarboxylase from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 283:5344-5354(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).
CC -!- FUNCTION: Decarboxylates branched-chain and aromatic alpha-keto acids
CC to aldehydes. {ECO:0000269|PubMed:18086676}.
CC -!- COFACTOR:
CC Name=a metal cation; Xref=ChEBI:CHEBI:25213; Evidence={ECO:0000250};
CC Note=Binds 1 metal ion per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000250};
CC Note=Binds 1 thiamine pyrophosphate per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Allosterically activated by alpha-keto acids and
CC the corresponding amino acids. L-leucine, L-valine, D-valine, L-
CC isoleucine, L-phenylalanine, D-phenylalanine, L-tyrosine and L-valine
CC are activators (with L-leucine and L-isoleucine being the strongest
CC activators) whereas L-tryptophan, tryptophol, phenylacetic acid and
CC indoleacetic acid have no effect.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.09 mM for indole pyruvate;
CC KM=1.17 mM for phenyl pyruvate;
CC KM=0.83 mM for alpha-keto caproate;
CC KM=1.21 mM for alpha-keto valerate;
CC KM=20.25 mM for alpha-keto-beta-methyl valerate;
CC KM=26.11 mM for benzoylformate;
CC KM=138.30 mM for alpha-keto-butyrate;
CC KM=0.40 mM for pyruvate;
CC Note=Pyruvate is converted with the lowest catalytic efficiency and
CC displays a weak substrate inhibition. The highest catalytic
CC efficiencies are found for indolepyruvate and alpha-ketoisocaproate.
CC The S0.5 values are 0.26 mM for indolepyruvate, 2.90 mM for alpha-
CC ketoisocaproate, 0.83 mM for phenylpyruvate, 0.92 mM for alpha-
CC ketocaproate, 1.31 mM for alpha-ketovalerate, 0.93 mM for 4-
CC hydroxyphenylpyruvate, 6.68 mM for alpha-keto-beta-methylvalerate,
CC 8.25 mM for benzoylformate, 5=14.17 mM for alpha-ketobutyrate, 24.47
CC mM for alpha-ketoisovalerate, 98.89 mM for pyruvate.;
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the TPP enzyme family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43601.1; -; Genomic_DNA.
DR PIR; E70814; E70814.
DR RefSeq; NP_215368.1; NC_000962.3.
DR RefSeq; WP_003900222.1; NZ_NVQJ01000040.1.
DR AlphaFoldDB; P9WG37; -.
DR SMR; P9WG37; -.
DR STRING; 83332.Rv0853c; -.
DR PaxDb; P9WG37; -.
DR DNASU; 885576; -.
DR GeneID; 885576; -.
DR KEGG; mtu:Rv0853c; -.
DR TubercuList; Rv0853c; -.
DR eggNOG; COG3961; Bacteria.
DR OMA; EQRYNDI; -.
DR PhylomeDB; P9WG37; -.
DR BRENDA; 4.1.1.72; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016831; F:carboxy-lyase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IEA:InterPro.
DR GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR012000; Thiamin_PyroP_enz_cen_dom.
DR InterPro; IPR012001; Thiamin_PyroP_enz_TPP-bd_dom.
DR InterPro; IPR000399; TPP-bd_CS.
DR InterPro; IPR012110; TPP_enzyme.
DR InterPro; IPR011766; TPP_enzyme-bd_C.
DR PANTHER; PTHR43452; PTHR43452; 1.
DR Pfam; PF02775; TPP_enzyme_C; 1.
DR Pfam; PF00205; TPP_enzyme_M; 1.
DR Pfam; PF02776; TPP_enzyme_N; 1.
DR PIRSF; PIRSF036565; Pyruvt_ip_decrb; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR SUPFAM; SSF52518; SSF52518; 2.
DR PROSITE; PS00187; TPP_ENZYMES; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; Decarboxylase; Lyase; Magnesium; Metal-binding;
KW Reference proteome; Thiamine pyrophosphate.
FT CHAIN 1..560
FT /note="Alpha-keto-acid decarboxylase"
FT /id="PRO_0000333751"
FT REGION 396..478
FT /note="Thiamine pyrophosphate binding"
FT /evidence="ECO:0000250"
FT BINDING 61
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 446
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 473
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 475
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
SQ SEQUENCE 560 AA; 59783 MW; F0430F720D57B7C4 CRC64;
MTPQKSDACS DPVYTVGDYL LDRLAELGVS EIFGVPGDYN LQFLDHIVAH PTIRWVGSAN
ELNAGYAADG YGRLRGMSAV VTTFGVGELS VTNAIAGSYA EHVPVVHIVG GPTKDAQGTR
RALHHSLGDG DFEHFLRISR EITCAQANLM PATAGREIDR VLSEVREQKR PGYILLSSDV
ARFPTEPPAA PLPRYPGGTS PRALSLFTKA AIELIADHQL TVLADLLVHR LQAVKELEAL
LAADVVPHAT LMWGKSLLDE SSPNFLGIYA GAASAERVRA AIEGAPVLVT AGVVFTDMVS
GFFSQRIDPA RTIDIGQYQS SVADQVFAPL EMSAALQALA TILTGRGISS PPVVPPPAEP
PPAMPARDEP LTQQMVWDRV CSALTPGNVV LADQGTSFYG MADHRLPQGV TFIGQPLWGS
IGYTLPAAVG AAVAHPDRRT VLLIGDGAAQ LTVQELGTFS REGLSPVIVV VNNDGYTVER
AIHGETAPYN DIVSWNWTEL PSALGVTNHL AFRAQTYGQL DDALTVAAAR RDRMVLVEVV
LPRLEIPRLL GQLVGSMAPQ
