DCDA_MYCTU
ID DCDA_MYCTU Reviewed; 447 AA.
AC P9WIU7; L0T7U9; P0A5M4; P31848;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Diaminopimelate decarboxylase {ECO:0000255|HAMAP-Rule:MF_02120};
DE Short=DAP decarboxylase {ECO:0000255|HAMAP-Rule:MF_02120};
DE Short=DAPDC {ECO:0000255|HAMAP-Rule:MF_02120};
DE EC=4.1.1.20 {ECO:0000255|HAMAP-Rule:MF_02120};
GN Name=lysA {ECO:0000255|HAMAP-Rule:MF_02120}; OrderedLocusNames=Rv1293;
GN ORFNames=MTCY373.13;
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 [GENOMIC DNA].
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=8440471; DOI=10.1016/0378-1119(93)90768-x;
RA Andersen A.B., Hansen E.B.;
RT "Cloning of the lysA gene from Mycobacterium tuberculosis.";
RL Gene 124:105-109(1993).
RN [2]
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 [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 CRYSTALLIZATION, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16511157; DOI=10.1107/s1744309105022839;
RA Kefala G., Perry L.J., Weiss M.S.;
RT "Cloning, expression, purification, crystallization and preliminary X-ray
RT diffraction analysis of LysA (Rv1293) from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 61:782-784(2005).
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]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEXES WITH PLP AND LYSINE,
RP FUNCTION, COFACTOR, SUBUNIT, DISULFIDE BOND, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12637582; DOI=10.1074/jbc.m301549200;
RA Gokulan K., Rupp B., Pavelka M.S. Jr., Jacobs W.R. Jr., Sacchettini J.C.;
RT "Crystal structure of Mycobacterium tuberculosis diaminopimelate
RT decarboxylase, an essential enzyme in bacterial lysine biosynthesis.";
RL J. Biol. Chem. 278:18588-18596(2003).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS), SUBUNIT, AND DISULFIDE BOND.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19543810; DOI=10.1007/s10969-009-9065-z;
RA Weyand S., Kefala G., Svergun D.I., Weiss M.S.;
RT "The three-dimensional structure of diaminopimelate decarboxylase from
RT Mycobacterium tuberculosis reveals a tetrameric enzyme organisation.";
RL J. Struct. Funct. Genomics 10:209-217(2009).
CC -!- FUNCTION: Specifically catalyzes the decarboxylation of meso-
CC diaminopimelate (meso-DAP) to L-lysine (Probable). Is essential for the
CC viability of M.tuberculosis in the host (PubMed:12637582).
CC {ECO:0000255|HAMAP-Rule:MF_02120, ECO:0000269|PubMed:12637582,
CC ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + meso-2,6-diaminoheptanedioate = CO2 + L-lysine;
CC Xref=Rhea:RHEA:15101, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:32551, ChEBI:CHEBI:57791; EC=4.1.1.20;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02120};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:12637582};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; L-lysine from DL-2,6-diaminopimelate: step 1/1.
CC {ECO:0000255|HAMAP-Rule:MF_02120}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Can also form homotetramer at
CC higher protein concentrations. {ECO:0000269|PubMed:12637582,
CC ECO:0000269|PubMed:16511157, ECO:0000269|PubMed:19543810}.
CC -!- DISRUPTION PHENOTYPE: Strains lacking this gene are lysine auxotrophs.
CC They cannot survive in immunocompromised mice.
CC {ECO:0000269|PubMed:12637582}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the Orn/Lys/Arg decarboxylase class-II family.
CC LysA subfamily. {ECO:0000255|HAMAP-Rule:MF_02120}.
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DR EMBL; M94109; AAA25361.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44050.1; -; Genomic_DNA.
DR PIR; A70773; A70773.
DR RefSeq; NP_215809.1; NC_000962.3.
DR RefSeq; WP_003406632.1; NZ_NVQJ01000030.1.
DR PDB; 1HKV; X-ray; 2.60 A; A/B=1-447.
DR PDB; 1HKW; X-ray; 2.80 A; A/B=1-447.
DR PDB; 2O0T; X-ray; 2.33 A; A/B/C/D=2-447.
DR PDBsum; 1HKV; -.
DR PDBsum; 1HKW; -.
DR PDBsum; 2O0T; -.
DR AlphaFoldDB; P9WIU7; -.
DR SMR; P9WIU7; -.
DR STRING; 83332.Rv1293; -.
DR PaxDb; P9WIU7; -.
DR DNASU; 886960; -.
DR GeneID; 45425267; -.
DR GeneID; 886960; -.
DR KEGG; mtu:Rv1293; -.
DR PATRIC; fig|83332.111.peg.1444; -.
DR TubercuList; Rv1293; -.
DR eggNOG; COG1166; Bacteria.
DR OMA; YCRSMAS; -.
DR PhylomeDB; P9WIU7; -.
DR BRENDA; 4.1.1.20; 3445.
DR UniPathway; UPA00034; UER00027.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0008836; F:diaminopimelate decarboxylase activity; IDA:MTBBASE.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:MTBBASE.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IDA:MTBBASE.
DR CDD; cd06828; PLPDE_III_DapDC; 1.
DR Gene3D; 2.40.37.10; -; 1.
DR Gene3D; 3.20.20.10; -; 1.
DR HAMAP; MF_02120; LysA; 1.
DR InterPro; IPR009006; Ala_racemase/Decarboxylase_C.
DR InterPro; IPR002986; DAP_deCOOHase_LysA.
DR InterPro; IPR022643; De-COase2_C.
DR InterPro; IPR022657; De-COase2_CS.
DR InterPro; IPR022644; De-COase2_N.
DR InterPro; IPR022653; De-COase2_pyr-phos_BS.
DR InterPro; IPR000183; Orn/DAP/Arg_de-COase.
DR InterPro; IPR029066; PLP-binding_barrel.
DR Pfam; PF02784; Orn_Arg_deC_N; 1.
DR Pfam; PF00278; Orn_DAP_Arg_deC; 1.
DR PRINTS; PR01181; DAPDCRBXLASE.
DR PRINTS; PR01179; ODADCRBXLASE.
DR SUPFAM; SSF50621; SSF50621; 2.
DR SUPFAM; SSF51419; SSF51419; 1.
DR TIGRFAMs; TIGR01048; lysA; 1.
DR PROSITE; PS00878; ODR_DC_2_1; 1.
DR PROSITE; PS00879; ODR_DC_2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Decarboxylase; Disulfide bond;
KW Lyase; Lysine biosynthesis; Pyridoxal phosphate; Reference proteome.
FT CHAIN 1..447
FT /note="Diaminopimelate decarboxylase"
FT /id="PRO_0000149929"
FT ACT_SITE 375
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02120"
FT BINDING 216
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12637582"
FT BINDING 258
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:12637582"
FT BINDING 300..303
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02120,
FT ECO:0000269|PubMed:12637582"
FT BINDING 303
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12637582"
FT BINDING 344
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12637582"
FT BINDING 348
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02120"
FT BINDING 376
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12637582"
FT BINDING 405
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:12637582"
FT BINDING 405
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12637582"
FT MOD_RES 72
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:12637582"
FT DISULFID 93
FT /note="Interchain (with C-375)"
FT /evidence="ECO:0000269|PubMed:12637582"
FT DISULFID 375
FT /note="Interchain (with C-72)"
FT /evidence="ECO:0000269|PubMed:19543810"
FT CONFLICT 346
FT /note="A -> G (in Ref. 1; AAA25361)"
FT /evidence="ECO:0000305"
FT CONFLICT 389..426
FT /note="DDIRPGDLVAVAATGAYCYSLSSRYNMVGRPAVVAVHA -> TIFGPAIWLR
FT LPPPALLLFAVESLQHGRPSRCGSGAR (in Ref. 1; AAA25361)"
FT /evidence="ECO:0000305"
FT TURN 9..11
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 31..38
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 40..46
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 47..60
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 77..86
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 89..92
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 95..103
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 120..129
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 139..152
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 156..163
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:2O0T"
FT TURN 187..190
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 191..201
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 203..211
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 222..246
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 272..289
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 303..306
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 310..323
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 329..336
FT /evidence="ECO:0007829|PDB:2O0T"
FT TURN 339..341
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 344..348
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 365..371
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 380..388
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 396..400
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 403..407
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 413..415
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 420..425
FT /evidence="ECO:0007829|PDB:2O0T"
FT STRAND 428..433
FT /evidence="ECO:0007829|PDB:2O0T"
FT HELIX 438..442
FT /evidence="ECO:0007829|PDB:2O0T"
SQ SEQUENCE 447 AA; 47458 MW; 3CE085A33F7F30F4 CRC64;
MNELLHLAPN VWPRNTTRDE VGVVCIAGIP LTQLAQEYGT PLFVIDEDDF RSRCRETAAA
FGSGANVHYA AKAFLCSEVA RWISEEGLCL DVCTGGELAV ALHASFPPER ITLHGNNKSV
SELTAAVKAG VGHIVVDSMT EIERLDAIAG EAGIVQDVLV RLTVGVEAHT HEFISTAHED
QKFGLSVASG AAMAAVRRVF ATDHLRLVGL HSHIGSQIFD VDGFELAAHR VIGLLRDVVG
EFGPEKTAQI ATVDLGGGLG ISYLPSDDPP PIAELAAKLG TIVSDESTAV GLPTPKLVVE
PGRAIAGPGT ITLYEVGTVK DVDVSATAHR RYVSVDGGMS DNIRTALYGA QYDVRLVSRV
SDAPPVPARL VGKHCESGDI IVRDTWVPDD IRPGDLVAVA ATGAYCYSLS SRYNMVGRPA
VVAVHAGNAR LVLRRETVDD LLSLEVR
