DAPD_MYCTU
ID DAPD_MYCTU Reviewed; 317 AA.
AC P9WP21; L0T666; O05302; Q7D8M6;
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=2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase {ECO:0000255|HAMAP-Rule:MF_02122};
DE EC=2.3.1.117 {ECO:0000269|PubMed:19394346};
DE AltName: Full=Tetrahydrodipicolinate N-succinyltransferase {ECO:0000255|HAMAP-Rule:MF_02122};
DE Short=THDP succinyltransferase {ECO:0000255|HAMAP-Rule:MF_02122};
DE Short=THP succinyltransferase {ECO:0000255|HAMAP-Rule:MF_02122};
DE AltName: Full=Tetrahydropicolinate succinylase {ECO:0000255|HAMAP-Rule:MF_02122};
GN Name=dapD {ECO:0000255|HAMAP-Rule:MF_02122}; OrderedLocusNames=Rv1201c;
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 CRYSTALLIZATION, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18765924; DOI=10.1107/s1744309108026559;
RA Schuldt L., Weyand S., Kefala G., Weiss M.S.;
RT "Cloning, expression, purification, crystallization and preliminary X-ray
RT diffraction analysis of tetrahydrodipicolinate-N-succinyltransferase
RT (Rv1201c) from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 64:863-866(2008).
RN [3]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
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 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 [5]
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) OF APOENZYME AND COMPLEX WITH
RP SUCCINYL-COA AND MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, ACTIVE SITE, REACTION MECHANISM, AND MUTAGENESIS OF GLU-199 AND
RP GLY-222.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19394346; DOI=10.1016/j.jmb.2009.04.046;
RA Schuldt L., Weyand S., Kefala G., Weiss M.S.;
RT "The three-dimensional structure of a mycobacterial DapD provides insights
RT into DapD diversity and reveals unexpected particulars about the enzymatic
RT mechanism.";
RL J. Mol. Biol. 389:863-879(2009).
CC -!- FUNCTION: Catalyzes the conversion of the cyclic tetrahydrodipicolinate
CC (THDP) into the acyclic N-succinyl-L-2-amino-6-oxopimelate using
CC succinyl-CoA. {ECO:0000269|PubMed:19394346}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2,3,4,5-tetrahydrodipicolinate + H2O + succinyl-CoA = (S)-
CC 2-succinylamino-6-oxoheptanedioate + CoA; Xref=Rhea:RHEA:17325,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15685, ChEBI:CHEBI:16845,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57292; EC=2.3.1.117;
CC Evidence={ECO:0000269|PubMed:19394346};
CC -!- ACTIVITY REGULATION: Is activated by Mg(2+), Ca(2+) and Mn(2+), and
CC inhibited by Zn(2+) and Co(2+). Is not inhibited by EDTA in vitro.
CC {ECO:0000269|PubMed:19394346}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; LL-2,6-diaminopimelate from (S)-tetrahydrodipicolinate
CC (succinylase route): step 1/3. {ECO:0000255|HAMAP-Rule:MF_02122}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:18765924}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_02122}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the type 2 tetrahydrodipicolinate N-
CC succinyltransferase family. {ECO:0000255|HAMAP-Rule:MF_02122}.
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DR EMBL; AL123456; CCP43957.1; -; Genomic_DNA.
DR PIR; G70608; G70608.
DR RefSeq; NP_215717.1; NC_000962.3.
DR RefSeq; WP_003898768.1; NZ_NVQJ01000039.1.
DR PDB; 3FSX; X-ray; 2.15 A; A/B/C/D/E=2-317.
DR PDB; 3FSY; X-ray; 1.97 A; A/B/C/D/E=2-317.
DR PDBsum; 3FSX; -.
DR PDBsum; 3FSY; -.
DR AlphaFoldDB; P9WP21; -.
DR SMR; P9WP21; -.
DR STRING; 83332.Rv1201c; -.
DR PaxDb; P9WP21; -.
DR DNASU; 886088; -.
DR GeneID; 886088; -.
DR KEGG; mtu:Rv1201c; -.
DR PATRIC; fig|83332.111.peg.1342; -.
DR TubercuList; Rv1201c; -.
DR eggNOG; COG2171; Bacteria.
DR OMA; TVLDTWF; -.
DR PhylomeDB; P9WP21; -.
DR BRENDA; 2.3.1.117; 3445.
DR UniPathway; UPA00034; UER00019.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008666; F:2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase activity; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0031402; F:sodium ion binding; IDA:MTBBASE.
DR GO; GO:0120226; F:succinyl-CoA binding; IDA:UniProtKB.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:UniProtKB-UniRule.
DR Gene3D; 3.30.60.70; -; 1.
DR HAMAP; MF_02122; DapD_type2; 1.
DR InterPro; IPR019875; DapD_actinobacteria.
DR InterPro; IPR001451; Hexapep.
DR InterPro; IPR032784; THDPS_M.
DR InterPro; IPR038361; THDPS_M_sf.
DR InterPro; IPR011004; Trimer_LpxA-like_sf.
DR InterPro; IPR026586; Type2_DapD.
DR Pfam; PF14602; Hexapep_2; 1.
DR Pfam; PF14789; THDPS_M; 1.
DR SUPFAM; SSF51161; SSF51161; 1.
DR TIGRFAMs; TIGR03535; DapD_actino; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Amino-acid biosynthesis; Cytoplasm;
KW Diaminopimelate biosynthesis; Lysine biosynthesis; Magnesium;
KW Metal-binding; Reference proteome; Transferase.
FT CHAIN 1..317
FT /note="2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-
FT succinyltransferase"
FT /id="PRO_0000412254"
FT ACT_SITE 199
FT /note="Acyl-anhydride intermediate"
FT /evidence="ECO:0000305|PubMed:19394346"
FT BINDING 166
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="ligand shared between trimeric partners"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 183
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="ligand shared between trimeric partners"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 201
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 216
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 219
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 242
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 257..258
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 265
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 277
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:19394346"
FT BINDING 290..293
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:19394346"
FT MUTAGEN 199
FT /note="E->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:19394346"
FT MUTAGEN 222
FT /note="G->P: Loss of activity."
FT /evidence="ECO:0000269|PubMed:19394346"
FT STRAND 5..15
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 21..25
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:3FSY"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:3FSY"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:3FSY"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 63..73
FT /evidence="ECO:0007829|PDB:3FSY"
FT HELIX 82..93
FT /evidence="ECO:0007829|PDB:3FSY"
FT HELIX 107..110
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:3FSY"
FT HELIX 127..134
FT /evidence="ECO:0007829|PDB:3FSY"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:3FSY"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:3FSY"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:3FSX"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:3FSY"
FT HELIX 278..281
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 285..291
FT /evidence="ECO:0007829|PDB:3FSY"
FT TURN 293..295
FT /evidence="ECO:0007829|PDB:3FSY"
FT STRAND 298..303
FT /evidence="ECO:0007829|PDB:3FSY"
SQ SEQUENCE 317 AA; 32642 MW; EF204F46B90ADFF3 CRC64;
MSTVTGAAGI GLATLAADGS VLDTWFPAPE LTESGTSATS RLAVSDVPVE LAALIGRDDD
RRTETIAVRT VIGSLDDVAA DPYDAYLRLH LLSHRLVAPH GLNAGGLFGV LTNVVWTNHG
PCAIDGFEAV RARLRRRGPV TVYGVDKFPR MVDYVVPTGV RIADADRVRL GAHLAPGTTV
MHEGFVNYNA GTLGASMVEG RISAGVVVGD GSDVGGGASI MGTLSGGGTH VISIGKRCLL
GANSGLGISL GDDCVVEAGL YVTAGTRVTM PDSNSVKARE LSGSSNLLFR RNSVSGAVEV
LARDGQGIAL NEDLHAN
