DAPDH_LYSSH
ID DAPDH_LYSSH Reviewed; 326 AA.
AC Q9KWR0;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Meso-diaminopimelate D-dehydrogenase;
DE Short=DAPDH;
DE Short=Meso-DAP dehydrogenase;
DE EC=1.4.1.16;
DE AltName: Full=Meso-alpha,epsilon-diaminopimelate D-dehydrogenase;
GN Name=dapdh;
OS Lysinibacillus sphaericus (Bacillus sphaericus).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Lysinibacillus.
OX NCBI_TaxID=1421;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 10208 / DSM 5019 / NBRC 3525 / NCIMB 11935 / NRS 966 / 1911;
RA Sakamoto S., Seki M., Nagata S., Misono H.;
RT "Cloning, sequencing, and expression of meso-diaminopimelate dehydrogenase
RT gene from Bacillus sphaericus.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RC STRAIN=ATCC 10208 / DSM 5019 / NBRC 3525 / NCIMB 11935 / NRS 966 / 1911;
RX PubMed=762012; DOI=10.1128/jb.137.1.22-27.1979;
RA Misono H., Togawa H., Yamamoto T., Soda K.;
RT "Meso-alpha,epsilon-diaminopimelate D-dehydrogenase: distribution and the
RT reaction product.";
RL J. Bacteriol. 137:22-27(1979).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, STEREOSPECIFICITY OF THE REACTION,
RP SUBUNIT, AND REACTION MECHANISM.
RC STRAIN=ATCC 10208 / DSM 5019 / NBRC 3525 / NCIMB 11935 / NRS 966 / 1911;
RX PubMed=7430138; DOI=10.1016/s0021-9258(19)70348-2;
RA Misono H., Soda K.;
RT "Properties of meso-alpha,epsilon-diaminopimelate D-dehydrogenase from
RT Bacillus sphaericus.";
RL J. Biol. Chem. 255:10599-10605(1980).
RN [4]
RP ACTIVITY REGULATION.
RC STRAIN=ATCC 10208 / DSM 5019 / NBRC 3525 / NCIMB 11935 / NRS 966 / 1911;
RX DOI=10.1039/A900297I;
RA Sutherland A., Caplan J.F., Vederas J.C.;
RT "Unsaturated alpha-aminopimelic acids as potent inhibitors of meso-
RT diaminopimelic acid (DAP) D-dehydrogenase.";
RL Chem. Commun. (Camb.) 6:555-556(1999).
CC -!- FUNCTION: Catalyzes the reversible NADPH-dependent reductive amination
CC of L-2-amino-6-oxopimelate, the acyclic form of L-
CC tetrahydrodipicolinate, to generate the meso compound, D,L-2,6-
CC diaminopimelate. Probably plays a role in lysine biosynthesis. Exhibits
CC a high substrate specificity, since alpha-ketoglutarate, pyruvate,
CC oxaloacetate, glyoxylate, alpha-ketobutyrate, alpha-ketovalerate,
CC alpha-ketocaproate, alpha-ketoisocaproate, alpha-ketoisovalerate, and
CC phenylpyruvate are not substrates for the reductive amination reaction,
CC and L,L-2,6-diaminopimelate, D,D-2,6-diaminopimelate, DL-alpha-
CC aminopimelate, meso- and DL-2,5-diaminoadipate, L-djenkolate, L-
CC cystine, L-lysine, S-(beta-aminoethy1)-L-homocysteine, L-ornithine, L-
CC arginine, L-alpha,gamma-diaminobutyrate, L-histidine, L-phenylalanine,
CC L-tyrosine, L-glutamate, L-aspartate, L-leucine, L-valine, L-
CC methionine, L-serine, L-alanine, L-alpha-aminobutyrate, D-lysine, D-
CC glutamate, D-leucine, D-alanine, D-phenylalanine, epsilon-
CC aminocaproate, 7-aminoheptanoate, and 8-aminooctanoate are not
CC substrates for the oxidative deamination reaction. Cannot use NAD(+) or
CC NAD(+) analogs instead of NADP(+) for the oxidative deamination
CC reaction. {ECO:0000269|PubMed:7430138, ECO:0000269|PubMed:762012}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + meso-2,6-diaminoheptanedioate + NADP(+) = (S)-2-amino-6-
CC oxoheptanedioate + H(+) + NADPH + NH4(+); Xref=Rhea:RHEA:13561,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57791, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58556; EC=1.4.1.16; Evidence={ECO:0000269|PubMed:7430138,
CC ECO:0000269|PubMed:762012};
CC -!- ACTIVITY REGULATION: L,L-2,6-diaminopimelate, D,D-2,6-diaminopimelate
CC and meso-2,5-diaminoadipate competitively inhibit the oxidation of
CC meso-2,6-diaminopimelate. L-2-amino-6-methylene-pimelate is also a
CC potent competitive inhibitor (5 uM) of this reaction. Glyoxylate
CC inhibits the reductive amination of L-2-amino-6-oxopimelate about 30%.
CC The enzyme is inhibited completely by p-chloromercuribenzoate and
CC HgCl(2) in vitro. {ECO:0000269|PubMed:7430138, ECO:0000269|Ref.4}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.5 mM for meso-2,6-diaminoheptanedioate
CC {ECO:0000269|PubMed:7430138};
CC KM=83 uM for NADP(+) {ECO:0000269|PubMed:7430138};
CC KM=0.20 mM for NADPH {ECO:0000269|PubMed:7430138};
CC KM=0.24 mM for L-2-amino-6-oxoheptanedioate
CC {ECO:0000269|PubMed:7430138};
CC KM=12.5 mM for ammonia {ECO:0000269|PubMed:7430138};
CC Note=The rate of the reductive amination reaction is about 11 times
CC higher than that of the oxidative deamination at pH 7.5.;
CC pH dependence:
CC Optimum pH is about 10.5 for the oxidative deamination of meso-
CC diaminopimelate and 7.5 for the reductive amination of L-2-amino-6-
CC oxopimelate. The rate of the amination reaction declines markedly
CC above pH 9.0. {ECO:0000269|PubMed:7430138};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; DL-2,6-diaminopimelate from (S)-tetrahydrodipicolinate: step
CC 1/1.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:7430138}.
CC -!- INDUCTION: Constitutively expressed. Not induced by meso-2,6-
CC diaminopimelate. {ECO:0000269|PubMed:762012}.
CC -!- MISCELLANEOUS: The reductive amination proceeds through a sequential
CC ordered ternary-binary mechanism. NADPH binds first to the enzyme
CC followed by L-2-amino-6-ketopimelate and ammonia, and the products are
CC released in the order of meso-2,6-diaminopimelate and NADP(+).
CC Moreover, the enzyme is B-stereospecific: the pro-S hydrogen at C-4 of
CC the dihydronicotinamide ring of NADPH is transferred to the substrate.
CC -!- SIMILARITY: Belongs to the diaminopimelate dehydrogenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB030649; BAB07799.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9KWR0; -.
DR SMR; Q9KWR0; -.
DR STRING; 1421.A2J09_08005; -.
DR KEGG; ag:BAB07799; -.
DR BioCyc; MetaCyc:MON-6607; -.
DR UniPathway; UPA00034; UER00026.
DR GO; GO:0008839; F:4-hydroxy-tetrahydrodipicolinate reductase; IEA:InterPro.
DR GO; GO:0047850; F:diaminopimelate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:UniProtKB-UniPathway.
DR InterPro; IPR000846; DapB_N.
DR InterPro; IPR010190; Diaminopimelate_DH_Ddh.
DR InterPro; IPR032094; Meso-DAP_DH_C.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01113; DapB_N; 1.
DR Pfam; PF16654; DAPDH_C; 1.
DR PIRSF; PIRSF025648; DDH; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01921; DAP-DH; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Diaminopimelate biosynthesis; Lysine biosynthesis;
KW NADP; Oxidoreductase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT CHAIN 2..326
FT /note="Meso-diaminopimelate D-dehydrogenase"
FT /id="PRO_5000049425"
FT BINDING 11..14
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 35..37
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 69..72
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 92..94
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 121..125
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 148
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 154..155
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 249
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 276
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 326 AA; 35576 MW; 1A4AF34D75654965 CRC64;
MSAIRVGIVG YGNLGRGVEF AISQNPDMEL VAVFTRRDPS TVSVASNASV YLVDDAEKFQ
DDIDVMILCG GSATDLPEQG PHFAQWFNTI DSFDTHAKIP EFFDAVDAAA QKSGKVSVIS
VGWDPGLFSL NRVLGEAVLP VGTTYTFWGD GLSQGHSDAV RRIEGVKNAV QYTLPIKDAV
ERVRNGENPE LTTREKHARE CWVVLEEGAD APKVEQEIVT MPNYFDEYNT TVNFISEDEF
NANHTGMPHG GFVIRSGESG ANDKQILEFS LKLESNPNFT SSVLVAYARA AHRLSQAGEK
GAKTVFDIPF GLLSPKSAAQ LRKELL
