MEND_MYCTU
ID MEND_MYCTU Reviewed; 554 AA.
AC P9WK11; L0T6U9; O06421; Q7D9N1;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 41.
DE RecName: Full=2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase {ECO:0000255|HAMAP-Rule:MF_01659};
DE Short=SEPHCHC synthase {ECO:0000255|HAMAP-Rule:MF_01659};
DE EC=2.2.1.9 {ECO:0000255|HAMAP-Rule:MF_01659};
DE AltName: Full=Menaquinone biosynthesis protein MenD {ECO:0000255|HAMAP-Rule:MF_01659};
GN Name=menD {ECO:0000255|HAMAP-Rule:MF_01659}; OrderedLocusNames=Rv0555;
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).
CC -!- FUNCTION: Catalyzes the thiamine diphosphate-dependent decarboxylation
CC of 2-oxoglutarate and the subsequent addition of the resulting succinic
CC semialdehyde-thiamine pyrophosphate anion to isochorismate to yield 2-
CC succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC).
CC {ECO:0000255|HAMAP-Rule:MF_01659}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + H(+) + isochorismate = 5-enolpyruvoyl-6-
CC hydroxy-2-succinyl-cyclohex-3-ene-1-carboxylate + CO2;
CC Xref=Rhea:RHEA:25593, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:29780, ChEBI:CHEBI:58818; EC=2.2.1.9;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01659};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01659};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01659};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01659};
CC Note=Binds 1 thiamine pyrophosphate per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_01659};
CC -!- PATHWAY: Quinol/quinone metabolism; 1,4-dihydroxy-2-naphthoate
CC biosynthesis; 1,4-dihydroxy-2-naphthoate from chorismate: step 2/7.
CC {ECO:0000255|HAMAP-Rule:MF_01659}.
CC -!- PATHWAY: Quinol/quinone metabolism; menaquinone biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_01659}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01659}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the TPP enzyme family. MenD subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01659}.
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DR EMBL; AL123456; CCP43293.1; -; Genomic_DNA.
DR PIR; F70548; F70548.
DR RefSeq; NP_215069.1; NC_000962.3.
DR RefSeq; WP_003402927.1; NZ_NVQJ01000036.1.
DR PDB; 5ERX; X-ray; 1.73 A; A=1-554.
DR PDB; 5ERY; X-ray; 2.25 A; A/B/C/D=1-554.
DR PDB; 5ESD; X-ray; 2.25 A; A/B/C/D=1-554.
DR PDB; 5ESO; X-ray; 2.05 A; A/B/C/D=1-554.
DR PDB; 5ESS; X-ray; 2.20 A; A/B/C/D=1-554.
DR PDB; 5ESU; X-ray; 2.20 A; A/B/C/D=1-554.
DR PDB; 6O04; X-ray; 2.50 A; A/B/C/D=1-554.
DR PDB; 6O0G; X-ray; 2.40 A; A/B/C/D=1-554.
DR PDB; 6O0J; X-ray; 2.35 A; A/B/C/D=1-554.
DR PDB; 6O0N; X-ray; 3.03 A; A/B/C/D=1-554.
DR PDBsum; 5ERX; -.
DR PDBsum; 5ERY; -.
DR PDBsum; 5ESD; -.
DR PDBsum; 5ESO; -.
DR PDBsum; 5ESS; -.
DR PDBsum; 5ESU; -.
DR PDBsum; 6O04; -.
DR PDBsum; 6O0G; -.
DR PDBsum; 6O0J; -.
DR PDBsum; 6O0N; -.
DR AlphaFoldDB; P9WK11; -.
DR SMR; P9WK11; -.
DR STRING; 83332.Rv0555; -.
DR PaxDb; P9WK11; -.
DR GeneID; 887554; -.
DR KEGG; mtu:Rv0555; -.
DR TubercuList; Rv0555; -.
DR eggNOG; COG1165; Bacteria.
DR OMA; FCNRGTS; -.
DR PhylomeDB; P9WK11; -.
DR BRENDA; 2.2.1.9; 3445.
DR UniPathway; UPA00079; -.
DR UniPathway; UPA01057; UER00164.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0070204; F:2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0030145; F:manganese ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009234; P:menaquinone biosynthetic process; IEA:UniProtKB-UniRule.
DR HAMAP; MF_01659; MenD; 1.
DR InterPro; IPR004433; MenaQ_synth_MenD.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR012001; Thiamin_PyroP_enz_TPP-bd_dom.
DR PANTHER; PTHR42916; PTHR42916; 2.
DR Pfam; PF02776; TPP_enzyme_N; 1.
DR PIRSF; PIRSF004983; MenD; 1.
DR SUPFAM; SSF52518; SSF52518; 2.
DR TIGRFAMs; TIGR00173; menD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Magnesium; Manganese; Menaquinone biosynthesis;
KW Metal-binding; Reference proteome; Thiamine pyrophosphate; Transferase.
FT CHAIN 1..554
FT /note="2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-
FT carboxylate synthase"
FT /id="PRO_0000341784"
FT HELIX 3..17
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 35..43
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 55..67
FT /evidence="ECO:0007829|PDB:5ERX"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:5ERY"
FT HELIX 82..96
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:5ESO"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:5ESO"
FT TURN 123..126
FT /evidence="ECO:0007829|PDB:5ESO"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 146..165
FT /evidence="ECO:0007829|PDB:5ERX"
FT TURN 166..169
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:5ESS"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:5ESO"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:5ESO"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 226..230
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:6O0N"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 261..266
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 282..288
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 295..298
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 311..322
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 326..349
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:5ERY"
FT HELIX 355..365
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 371..374
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 378..386
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:5ERX"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 407..425
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 434..439
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 440..445
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 447..450
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 460..470
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 473..477
FT /evidence="ECO:0007829|PDB:5ESO"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:5ESO"
FT HELIX 483..485
FT /evidence="ECO:0007829|PDB:5ESO"
FT HELIX 488..492
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 501..507
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 511..514
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 517..519
FT /evidence="ECO:0007829|PDB:5ERX"
FT HELIX 520..525
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 530..537
FT /evidence="ECO:0007829|PDB:5ERX"
FT STRAND 539..542
FT /evidence="ECO:0007829|PDB:6O0J"
FT HELIX 543..553
FT /evidence="ECO:0007829|PDB:5ERX"
SQ SEQUENCE 554 AA; 57836 MW; 879423AAB00F36A5 CRC64;
MNPSTTQARV VVDELIRGGV RDVVLCPGSR NAPLAFALQD ADRSGRIRLH VRIDERTAGY
LAIGLAIGAG APVCVAMTSG TAVANLGPAV VEANYARVPL IVLSANRPYE LLGTGANQTM
EQLGYFGTQV RASISLGLAE DAPERTSALN ATWRSATCRV LAAATGARTA NAGPVHFDIP
LREPLVPDPE PLGAVTPPGR PAGKPWTYTP PVTFDQPLDI DLSVDTVVIS GHGAGVHPNL
AALPTVAEPT APRSGDNPLH PLALPLLRPQ QVIMLGRPTL HRPVSVLLAD AEVPVFALTT
GPRWPDVSGN SQATGTRAVT TGAPRPAWLD RCAAMNRHAI AAVREQLAAH PLTTGLHVAA
AVSHALRPGD QLVLGASNPV RDVALAGLDT RGIRVRSNRG VAGIDGTVST AIGAALAYEG
AHERTGSPDS PPRTIALIGD LTFVHDSSGL LIGPTEPIPR SLTIVVSNDN GGGIFELLEQ
GDPRFSDVSS RIFGTPHDVD VGALCRAYHV ESRQIEVDEL GPTLDQPGAG MRVLEVKADR
SSLRQLHAAI KAAL
