Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

4-hydroxy-tetrahydrodipicolinate reductase

Gene

dapB

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate (Probable). Can use both NADH and NADPH as a reductant, with NADH being 6-fold as effective as NADPH.UniRule annotationCurated1 Publication

Catalytic activityi

(S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + NAD(P)+ + H2O = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + NAD(P)H.UniRule annotation

Kineticsi

  1. KM=3.2 µM for NADH1 Publication
  2. KM=11.8 µM for NADPH1 Publication

    Pathwayi: L-lysine biosynthesis via DAP pathway

    This protein is involved in step 4 of the subpathway that synthesizes (S)-tetrahydrodipicolinate from L-aspartate.UniRule annotation
    Proteins known to be involved in the 4 steps of the subpathway in this organism are:
    1. Aspartokinase (ask), Aspartokinase (LH57_20215)
    2. Aspartate-semialdehyde dehydrogenase (asd), Aspartate-semialdehyde dehydrogenase (asd)
    3. 4-hydroxy-tetrahydrodipicolinate synthase (dapA), 4-hydroxy-tetrahydrodipicolinate synthase (dapA)
    4. 4-hydroxy-tetrahydrodipicolinate reductase (dapB), 4-hydroxy-tetrahydrodipicolinate reductase (dapB)
    This subpathway is part of the pathway L-lysine biosynthesis via DAP pathway, which is itself part of Amino-acid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-tetrahydrodipicolinate from L-aspartate, the pathway L-lysine biosynthesis via DAP pathway and in Amino-acid biosynthesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei33 – 331NADUniRule annotation1 Publication
    Active sitei132 – 1321Proton donor/acceptorUniRule annotation
    Binding sitei133 – 1331Substrate
    Active sitei136 – 1361Proton donorCurated

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi7 – 126NAD(P)UniRule annotation1 Publication
    Nucleotide bindingi75 – 773NAD(P)UniRule annotation1 Publication
    Nucleotide bindingi102 – 1054NAD(P)UniRule annotation1 Publication

    GO - Molecular functioni

    • 4-hydroxy-tetrahydrodipicolinate reductase Source: MTBBASE
    • NADH binding Source: MTBBASE
    • NADPH binding Source: MTBBASE
    • oxidoreductase activity, acting on CH or CH2 groups, NAD or NADP as acceptor Source: UniProtKB-HAMAP

    GO - Biological processi

    • diaminopimelate biosynthetic process Source: MTBBASE
    • lysine biosynthetic process via diaminopimelate Source: MTBBASE
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Amino-acid biosynthesis, Diaminopimelate biosynthesis, Lysine biosynthesis

    Keywords - Ligandi

    NAD, NADP

    Enzyme and pathway databases

    UniPathwayiUPA00034; UER00018.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    4-hydroxy-tetrahydrodipicolinate reductaseUniRule annotation (EC:1.17.1.8UniRule annotation)
    Short name:
    HTPA reductaseUniRule annotation
    Gene namesi
    Name:dapBUniRule annotation
    Ordered Locus Names:Rv2773c
    ORF Names:MTV002.38c
    OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    Taxonomic identifieri83332 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    Proteomesi
    • UP000001584 Componenti: Chromosome

    Organism-specific databases

    TubercuListiRv2773c.

    Subcellular locationi

    • Cytoplasm UniRule annotation

    GO - Cellular componenti

    • cell wall Source: MTBBASE
    • cytosol Source: GO_Central
    • plasma membrane Source: MTBBASE
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi9 – 91K → A: Increases the nucleotide specificity from 6:1 for the wild-type enzyme to 34:1, due to a 4-fold decrease in NADPH affinity while the affinity for NADH remains nearly unchanged. 1 Publication
    Mutagenesisi11 – 111K → A: 2.8-fold increase in catalytic activity with NADH as substrate, while the affinity for NADH is essentially unaffected. 70-fold decrease in affinity for NADPH, causing the nucleotide specificity to increase from 6:1 for the wild-type enzyme to 187:1. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 2452454-hydroxy-tetrahydrodipicolinate reductasePRO_0000141458Add
    BLAST

    Proteomic databases

    PaxDbiP9WP23.

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation3 Publications

    Protein-protein interaction databases

    STRINGi83332.Rv2773c.

    Structurei

    Secondary structure

    1
    245
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi2 – 65Combined sources
    Turni7 – 93Combined sources
    Helixi11 – 2212Combined sources
    Beta strandi27 – 326Combined sources
    Beta strandi34 – 363Combined sources
    Helixi39 – 435Combined sources
    Beta strandi48 – 514Combined sources
    Turni55 – 573Combined sources
    Helixi58 – 6710Combined sources
    Beta strandi71 – 744Combined sources
    Helixi81 – 9212Combined sources
    Beta strandi98 – 1014Combined sources
    Helixi107 – 11913Combined sources
    Helixi120 – 1223Combined sources
    Beta strandi124 – 1329Combined sources
    Beta strandi138 – 1403Combined sources
    Helixi142 – 15413Combined sources
    Turni155 – 1573Combined sources
    Turni170 – 1734Combined sources
    Beta strandi175 – 1773Combined sources
    Beta strandi180 – 1867Combined sources
    Beta strandi192 – 2009Combined sources
    Beta strandi203 – 2119Combined sources
    Helixi214 – 2174Combined sources
    Helixi218 – 22710Combined sources
    Helixi228 – 2303Combined sources
    Beta strandi233 – 2386Combined sources
    Helixi239 – 2424Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1C3VX-ray2.39A/B1-245[»]
    1P9LX-ray2.30A/B1-245[»]
    1YL5X-ray2.30A/B2-245[»]
    1YL6X-ray2.90A/B2-245[»]
    1YL7X-ray2.34A/B/C/D/E/F/G/H2-245[»]
    ProteinModelPortaliP9WP23.
    SMRiP9WP23. Positions 2-245.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni142 – 1432Substrate binding

    Sequence similaritiesi

    Belongs to the DapB family.UniRule annotation

    Phylogenomic databases

    eggNOGiENOG4105DUK. Bacteria.
    COG0289. LUCA.
    KOiK00215.
    OMAiEAHHRMK.
    PhylomeDBiP9WP23.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    HAMAPiMF_00102. DapB.
    InterProiIPR022663. DapB_C.
    IPR000846. DapB_N.
    IPR022664. DapB_N_CS.
    IPR023940. DHDPR_bac.
    IPR016040. NAD(P)-bd_dom.
    [Graphical view]
    PANTHERiPTHR20836. PTHR20836. 1 hit.
    PfamiPF05173. DapB_C. 1 hit.
    PF01113. DapB_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000161. DHPR. 1 hit.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    TIGRFAMsiTIGR00036. dapB. 1 hit.
    PROSITEiPS01298. DAPB. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P9WP23-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MRVGVLGAKG KVGATMVRAV AAADDLTLSA ELDAGDPLSL LTDGNTEVVI
    60 70 80 90 100
    DFTHPDVVMG NLEFLIDNGI HAVVGTTGFT AERFQQVESW LVAKPNTSVL
    110 120 130 140 150
    IAPNFAIGAV LSMHFAKQAA RFFDSAEVIE LHHPHKADAP SGTAARTAKL
    160 170 180 190 200
    IAEARKGLPP NPDATSTSLP GARGADVDGI PVHAVRLAGL VAHQEVLFGT
    210 220 230 240
    EGETLTIRHD SLDRTSFVPG VLLAVRRIAE RPGLTVGLEP LLDLH
    Length:245
    Mass (Da):25,733
    Last modified:April 16, 2014 - v1
    Checksum:iCDB8273AFFD4C095
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti14 – 141A → T in AAC45142 (PubMed:9098082).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U66101 Genomic DNA. Translation: AAC45142.1.
    AL123456 Genomic DNA. Translation: CCP45572.1.
    PIRiD70882.
    RefSeqiNP_217289.1. NC_000962.3.
    WP_003414099.1. NZ_KK339370.1.

    Genome annotation databases

    EnsemblBacteriaiCCP45572; CCP45572; Rv2773c.
    GeneIDi888443.
    KEGGimtu:Rv2773c.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U66101 Genomic DNA. Translation: AAC45142.1.
    AL123456 Genomic DNA. Translation: CCP45572.1.
    PIRiD70882.
    RefSeqiNP_217289.1. NC_000962.3.
    WP_003414099.1. NZ_KK339370.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1C3VX-ray2.39A/B1-245[»]
    1P9LX-ray2.30A/B1-245[»]
    1YL5X-ray2.30A/B2-245[»]
    1YL6X-ray2.90A/B2-245[»]
    1YL7X-ray2.34A/B/C/D/E/F/G/H2-245[»]
    ProteinModelPortaliP9WP23.
    SMRiP9WP23. Positions 2-245.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv2773c.

    Proteomic databases

    PaxDbiP9WP23.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCCP45572; CCP45572; Rv2773c.
    GeneIDi888443.
    KEGGimtu:Rv2773c.

    Organism-specific databases

    TubercuListiRv2773c.

    Phylogenomic databases

    eggNOGiENOG4105DUK. Bacteria.
    COG0289. LUCA.
    KOiK00215.
    OMAiEAHHRMK.
    PhylomeDBiP9WP23.

    Enzyme and pathway databases

    UniPathwayiUPA00034; UER00018.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    HAMAPiMF_00102. DapB.
    InterProiIPR022663. DapB_C.
    IPR000846. DapB_N.
    IPR022664. DapB_N_CS.
    IPR023940. DHDPR_bac.
    IPR016040. NAD(P)-bd_dom.
    [Graphical view]
    PANTHERiPTHR20836. PTHR20836. 1 hit.
    PfamiPF05173. DapB_C. 1 hit.
    PF01113. DapB_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000161. DHPR. 1 hit.
    SUPFAMiSSF51735. SSF51735. 1 hit.
    TIGRFAMsiTIGR00036. dapB. 1 hit.
    PROSITEiPS01298. DAPB. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Cloning of the dapB gene, encoding dihydrodipicolinate reductase, from Mycobacterium tuberculosis."
      Pavelka M.S. Jr., Weisbrod T.R., Jacobs W.R. Jr.
      J. Bacteriol. 179:2777-2782(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: ATCC 25618 / H37Rv.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 25618 / H37Rv.
    3. "Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DapB (Rv2773c) from Mycobacterium tuberculosis."
      Kefala G., Janowski R., Panjikar S., Mueller-Dieckmann C., Weiss M.S.
      Acta Crystallogr. F 61:718-721(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: CRYSTALLIZATION, SUBUNIT.
      Strain: ATCC 25618 / H37Rv.
    4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Strain: ATCC 25618 / H37Rv.
    5. "The three-dimensional structures of the Mycobacterium tuberculosis dihydrodipicolinate reductase-NADH-2,6-PDC and -NADPH-2,6-PDC complexes. Structural and mutagenic analysis of relaxed nucleotide specificity."
      Cirilli M., Zheng R., Scapin G., Blanchard J.S.
      Biochemistry 42:10644-10650(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH NADH OR NADPH AND A SUBSTRATE ANALOG INHIBITOR, FUNCTION, KINETIC PARAMETERS, SUBSTRATE SPECIFICITY, SUBUNIT, MUTAGENESIS OF LYS-9 AND LYS-11.
      Strain: ATCC 25618 / H37Rv.
    6. "The structure of dihydrodipicolinate reductase (DapB) from Mycobacterium tuberculosis in three crystal forms."
      Janowski R., Kefala G., Weiss M.S.
      Acta Crystallogr. D 66:61-72(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 2-245 OF APOENZYME AND IN COMPLEX WITH NADH.
      Strain: ATCC 25618 / H37Rv.

    Entry informationi

    Entry nameiDAPB_MYCTU
    AccessioniPrimary (citable) accession number: P9WP23
    Secondary accession number(s): L0TDI3, O33315, P72024
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2014
    Last sequence update: April 16, 2014
    Last modified: January 20, 2016
    This is version 18 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Caution

    Was originally thought to be a dihydrodipicolinate reductase (DHDPR), catalyzing the conversion of dihydrodipicolinate to tetrahydrodipicolinate. However, it was shown in E.coli that the substrate of the enzymatic reaction is not dihydrodipicolinate (DHDP) but in fact (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid (HTPA), the product released by the DapA-catalyzed reaction.Curated

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
      Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.