DAPB_MYCTU
ID DAPB_MYCTU Reviewed; 245 AA.
AC P9WP23; L0TDI3; O33315; P72024;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=4-hydroxy-tetrahydrodipicolinate reductase {ECO:0000255|HAMAP-Rule:MF_00102};
DE Short=HTPA reductase {ECO:0000255|HAMAP-Rule:MF_00102};
DE EC=1.17.1.8 {ECO:0000255|HAMAP-Rule:MF_00102};
GN Name=dapB {ECO:0000255|HAMAP-Rule:MF_00102}; OrderedLocusNames=Rv2773c;
GN ORFNames=MTV002.38c;
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 25618 / H37Rv;
RX PubMed=9098082; DOI=10.1128/jb.179.8.2777-2782.1997;
RA Pavelka M.S. Jr., Weisbrod T.R., Jacobs W.R. Jr.;
RT "Cloning of the dapB gene, encoding dihydrodipicolinate reductase, from
RT Mycobacterium tuberculosis.";
RL J. Bacteriol. 179:2777-2782(1997).
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 CRYSTALLIZATION, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16511139; DOI=10.1107/s174430910501938x;
RA Kefala G., Janowski R., Panjikar S., Mueller-Dieckmann C., Weiss M.S.;
RT "Cloning, expression, purification, crystallization and preliminary X-ray
RT diffraction analysis of DapB (Rv2773c) from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 61:718-721(2005).
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] {ECO:0007744|PDB:1C3V, ECO:0007744|PDB:1P9L}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH NADH OR NADPH AND A
RP SUBSTRATE ANALOG INHIBITOR, FUNCTION, KINETIC PARAMETERS, SUBSTRATE
RP SPECIFICITY, SUBUNIT, AND MUTAGENESIS OF LYS-9 AND LYS-11.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12962488; DOI=10.1021/bi030044v;
RA Cirilli M., Zheng R., Scapin G., Blanchard J.S.;
RT "The three-dimensional structures of the Mycobacterium tuberculosis
RT dihydrodipicolinate reductase-NADH-2,6-PDC and -NADPH-2,6-PDC complexes.
RT Structural and mutagenic analysis of relaxed nucleotide specificity.";
RL Biochemistry 42:10644-10650(2003).
RN [6] {ECO:0007744|PDB:1YL5, ECO:0007744|PDB:1YL6, ECO:0007744|PDB:1YL7}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 2-245 OF APOENZYME AND IN COMPLEX
RP WITH NADH.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20057050; DOI=10.1107/s0907444909043960;
RA Janowski R., Kefala G., Weiss M.S.;
RT "The structure of dihydrodipicolinate reductase (DapB) from Mycobacterium
RT tuberculosis in three crystal forms.";
RL Acta Crystallogr. D 66:61-72(2010).
CC -!- FUNCTION: Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate
CC (HTPA) to tetrahydrodipicolinate (Probable). Can use both NADH and
CC NADPH as a reductant, with NADH being 6-fold as effective as NADPH.
CC {ECO:0000255|HAMAP-Rule:MF_00102, ECO:0000269|PubMed:12962488,
CC ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2,3,4,5-tetrahydrodipicolinate + H2O + NAD(+) = (2S,4S)-4-
CC hydroxy-2,3,4,5-tetrahydrodipicolinate + H(+) + NADH;
CC Xref=Rhea:RHEA:35323, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16845, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:67139; EC=1.17.1.8; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00102};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2,3,4,5-tetrahydrodipicolinate + H2O + NADP(+) = (2S,4S)-
CC 4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H(+) + NADPH;
CC Xref=Rhea:RHEA:35331, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16845, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:67139; EC=1.17.1.8; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00102};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.2 uM for NADH {ECO:0000269|PubMed:12962488};
CC KM=11.8 uM for NADPH {ECO:0000269|PubMed:12962488};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 4/4.
CC {ECO:0000255|HAMAP-Rule:MF_00102}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_00102,
CC ECO:0000269|PubMed:12962488, ECO:0000269|PubMed:16511139,
CC ECO:0000269|PubMed:20057050}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00102}.
CC -!- SIMILARITY: Belongs to the DapB family. {ECO:0000255|HAMAP-
CC Rule:MF_00102}.
CC -!- CAUTION: Was originally thought to be a dihydrodipicolinate reductase
CC (DHDPR), catalyzing the conversion of dihydrodipicolinate to
CC tetrahydrodipicolinate. However, it was shown in E.coli that the
CC substrate of the enzymatic reaction is not dihydrodipicolinate (DHDP)
CC but in fact (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid
CC (HTPA), the product released by the DapA-catalyzed reaction.
CC {ECO:0000305}.
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DR EMBL; U66101; AAC45142.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP45572.1; -; Genomic_DNA.
DR PIR; D70882; D70882.
DR RefSeq; NP_217289.1; NC_000962.3.
DR RefSeq; WP_003414099.1; NZ_NVQJ01000020.1.
DR PDB; 1C3V; X-ray; 2.39 A; A/B=1-245.
DR PDB; 1P9L; X-ray; 2.30 A; A/B=1-245.
DR PDB; 1YL5; X-ray; 2.30 A; A/B=2-245.
DR PDB; 1YL6; X-ray; 2.90 A; A/B=2-245.
DR PDB; 1YL7; X-ray; 2.34 A; A/B/C/D/E/F/G/H=2-245.
DR PDB; 5TEK; X-ray; 2.01 A; A/B=1-245.
DR PDB; 5TJY; X-ray; 2.40 A; A=1-244.
DR PDB; 5TJZ; X-ray; 1.50 A; A=1-244.
DR PDB; 5UGV; X-ray; 2.25 A; A/B=1-245.
DR PDBsum; 1C3V; -.
DR PDBsum; 1P9L; -.
DR PDBsum; 1YL5; -.
DR PDBsum; 1YL6; -.
DR PDBsum; 1YL7; -.
DR PDBsum; 5TEK; -.
DR PDBsum; 5TJY; -.
DR PDBsum; 5TJZ; -.
DR PDBsum; 5UGV; -.
DR AlphaFoldDB; P9WP23; -.
DR SMR; P9WP23; -.
DR STRING; 83332.Rv2773c; -.
DR DrugBank; DB04267; Dipicolinic acid.
DR PaxDb; P9WP23; -.
DR DNASU; 888443; -.
DR GeneID; 45426762; -.
DR GeneID; 888443; -.
DR KEGG; mtu:Rv2773c; -.
DR TubercuList; Rv2773c; -.
DR eggNOG; COG0289; Bacteria.
DR OMA; HHPNKAD; -.
DR PhylomeDB; P9WP23; -.
DR BioCyc; MetaCyc:G185E-7022-MON; -.
DR BRENDA; 1.17.1.8; 3445.
DR SABIO-RK; P9WP23; -.
DR UniPathway; UPA00034; UER00018.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008839; F:4-hydroxy-tetrahydrodipicolinate reductase; IDA:MTBBASE.
DR GO; GO:0070404; F:NADH binding; IDA:MTBBASE.
DR GO; GO:0070402; F:NADPH binding; IDA:MTBBASE.
DR GO; GO:0016726; F:oxidoreductase activity, acting on CH or CH2 groups, NAD or NADP as acceptor; IEA:UniProtKB-UniRule.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IDA:MTBBASE.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IDA:MTBBASE.
DR HAMAP; MF_00102; DapB; 1.
DR InterPro; IPR022663; DapB_C.
DR InterPro; IPR000846; DapB_N.
DR InterPro; IPR022664; DapB_N_CS.
DR InterPro; IPR023940; DHDPR_bac.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR20836; PTHR20836; 1.
DR Pfam; PF05173; DapB_C; 1.
DR Pfam; PF01113; DapB_N; 1.
DR PIRSF; PIRSF000161; DHPR; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00036; dapB; 1.
DR PROSITE; PS01298; DAPB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Cytoplasm;
KW Diaminopimelate biosynthesis; Lysine biosynthesis; NAD; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..245
FT /note="4-hydroxy-tetrahydrodipicolinate reductase"
FT /id="PRO_0000141458"
FT ACT_SITE 132
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00102"
FT ACT_SITE 136
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT BINDING 11..12
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0000269|PubMed:20057050, ECO:0007744|PDB:1P9L,
FT ECO:0007744|PDB:1YL7"
FT BINDING 11..12
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0007744|PDB:1C3V"
FT BINDING 33
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0000269|PubMed:20057050, ECO:0007744|PDB:1P9L,
FT ECO:0007744|PDB:1YL7"
FT BINDING 75..77
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0000269|PubMed:20057050, ECO:0007744|PDB:1P9L,
FT ECO:0007744|PDB:1YL7"
FT BINDING 75..77
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0007744|PDB:1C3V"
FT BINDING 102..105
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0000269|PubMed:20057050, ECO:0007744|PDB:1P9L,
FT ECO:0007744|PDB:1YL7"
FT BINDING 102..105
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0007744|PDB:1C3V"
FT BINDING 133
FT /ligand="(S)-2,3,4,5-tetrahydrodipicolinate"
FT /ligand_id="ChEBI:CHEBI:16845"
FT /evidence="ECO:0000305|PubMed:12962488,
FT ECO:0007744|PDB:1C3V, ECO:0007744|PDB:1P9L"
FT BINDING 136
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0000269|PubMed:20057050, ECO:0007744|PDB:1P9L"
FT BINDING 136
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12962488,
FT ECO:0007744|PDB:1C3V"
FT BINDING 142..143
FT /ligand="(S)-2,3,4,5-tetrahydrodipicolinate"
FT /ligand_id="ChEBI:CHEBI:16845"
FT /evidence="ECO:0000305|PubMed:12962488,
FT ECO:0007744|PDB:1C3V, ECO:0007744|PDB:1P9L"
FT MUTAGEN 9
FT /note="K->A: Increases the nucleotide specificity from 6:1
FT for the wild-type enzyme to 34:1, due to a 4-fold decrease
FT in NADPH affinity while the affinity for NADH remains
FT nearly unchanged."
FT /evidence="ECO:0000269|PubMed:12962488"
FT MUTAGEN 11
FT /note="K->A: 2.8-fold increase in catalytic activity with
FT NADH as substrate, while the affinity for NADH is
FT essentially unaffected. 70-fold decrease in affinity for
FT NADPH, causing the nucleotide specificity to increase from
FT 6:1 for the wild-type enzyme to 187:1."
FT /evidence="ECO:0000269|PubMed:12962488"
FT CONFLICT 14
FT /note="A -> T (in Ref. 1; AAC45142)"
FT /evidence="ECO:0000305"
FT STRAND 1..6
FT /evidence="ECO:0007829|PDB:5TJZ"
FT TURN 7..9
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 11..22
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 26..32
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1C3V"
FT HELIX 39..43
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:5TJZ"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 58..67
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 107..119
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 124..132
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:5UGV"
FT HELIX 142..154
FT /evidence="ECO:0007829|PDB:5TJZ"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:5TJZ"
FT TURN 170..173
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 180..186
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 192..200
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 203..211
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 218..227
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:5TJZ"
FT STRAND 233..238
FT /evidence="ECO:0007829|PDB:5TJZ"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:5TJZ"
SQ SEQUENCE 245 AA; 25733 MW; CDB8273AFFD4C095 CRC64;
MRVGVLGAKG KVGATMVRAV AAADDLTLSA ELDAGDPLSL LTDGNTEVVI DFTHPDVVMG
NLEFLIDNGI HAVVGTTGFT AERFQQVESW LVAKPNTSVL IAPNFAIGAV LSMHFAKQAA
RFFDSAEVIE LHHPHKADAP SGTAARTAKL IAEARKGLPP NPDATSTSLP GARGADVDGI
PVHAVRLAGL VAHQEVLFGT EGETLTIRHD SLDRTSFVPG VLLAVRRIAE RPGLTVGLEP
LLDLH
