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Database: UniProt
Entry: P44514
LinkDB: P44514
Original site: P44514 
ID   DAPE_HAEIN              Reviewed;         377 AA.
AC   P44514;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   01-OCT-2014, entry version 101.
DE   RecName: Full=Succinyl-diaminopimelate desuccinylase;
DE            Short=SDAP desuccinylase;
DE            EC=3.5.1.18;
DE   AltName: Full=N-succinyl-LL-2,6-diaminoheptanedioate amidohydrolase;
GN   Name=dapE; OrderedLocusNames=HI_0102;
OS   Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC   Pasteurellaceae; Haemophilus.
OX   NCBI_TaxID=71421;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX   PubMed=7542800; DOI=10.1126/science.7542800;
RA   Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F.,
RA   Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M.,
RA   McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D.,
RA   Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M.,
RA   Weidman J.F., Phillips C.A., Spriggs T., Hedblom E., Cotton M.D.,
RA   Utterback T.R., Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C.,
RA   Fine L.D., Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M.,
RA   Gnehm C.L., McDonald L.A., Small K.V., Fraser C.M., Smith H.O.,
RA   Venter J.C.;
RT   "Whole-genome random sequencing and assembly of Haemophilus influenzae
RT   Rd.";
RL   Science 269:496-512(1995).
RN   [2]
RP   PROTEIN SEQUENCE OF 1-10, MASS SPECTROMETRY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, AND ENZYME REGULATION.
RX   PubMed=9671518; DOI=10.1021/bi9806807;
RA   Born T.L., Zheng R., Blanchard J.S.;
RT   "Hydrolysis of N-succinyl-L,L-diaminopimelic acid by the Haemophilus
RT   influenzae dapE-encoded desuccinylase: metal activation, solvent
RT   isotope effects, and kinetic mechanism.";
RL   Biochemistry 37:10478-10487(1998).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP   SPECIFICITY, AND COFACTOR.
RX   PubMed=12962500; DOI=10.1021/bi034845+;
RA   Bienvenue D.L., Gilner D.M., Davis R.S., Bennett B., Holz R.C.;
RT   "Substrate specificity, metal binding properties, and spectroscopic
RT   characterization of the DapE-encoded N-succinyl-L,L-diaminopimelic
RT   acid desuccinylase from Haemophilus influenzae.";
RL   Biochemistry 42:10756-10763(2003).
RN   [4]
RP   COFACTOR, AND ENZYME REGULATION.
RX   PubMed=14640610; DOI=10.1021/ja036650v;
RA   Cosper N.J., Bienvenue D.L., Shokes J.E., Gilner D.M., Tsukamoto T.,
RA   Scott R.A., Holz R.C.;
RT   "The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase
RT   from Haemophilus influenzae is a dinuclear metallohydrolase.";
RL   J. Am. Chem. Soc. 125:14654-14655(2003).
RN   [5]
RP   FUNCTION, MUTAGENESIS OF GLU-134, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   REACTIONJ MECHANISM.
RX   PubMed=16421726; DOI=10.1007/s00775-005-0071-8;
RA   Davis R., Bienvenue D., Swierczek S.I., Gilner D.M., Rajagopal L.,
RA   Bennett B., Holz R.C.;
RT   "Kinetic and spectroscopic characterization of the E134A- and E134D-
RT   altered dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase
RT   from Haemophilus influenzae.";
RL   J. Biol. Inorg. Chem. 11:206-216(2006).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-67 AND HIS-349, AND
RP   COFACTOR.
RX   PubMed=18712420; DOI=10.1007/s00775-008-0418-z;
RA   Gillner D.M., Bienvenue D.L., Nocek B.P., Joachimiak A., Zachary V.,
RA   Bennett B., Holz R.C.;
RT   "The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase
RT   from Haemophilus influenzae contains two active-site histidine
RT   residues.";
RL   J. Biol. Inorg. Chem. 14:1-10(2009).
RN   [7]
RP   ENZYME REGULATION.
RX   PubMed=21577314; DOI=10.1155/2011/306465;
RA   Uda N.R., Creus M.;
RT   "Selectivity of inhibition of N-succinyl-L,L-diaminopimelic acid
RT   desuccinylase in bacteria: The product of dapE-gene is not the target
RT   of L-captopril antimicrobial activity.";
RL   Bioinorg. Chem. Appl. 2011:306465-306465(2011).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH ZINC IONS,
RP   COFACTOR, REACTIONJ MECHANISM, ACTIVE SITE, AND SUBUNIT.
RX   PubMed=20138056; DOI=10.1016/j.jmb.2010.01.062;
RA   Nocek B.P., Gillner D.M., Fan Y., Holz R.C., Joachimiak A.;
RT   "Structural basis for catalysis by the mono- and dimetalated forms of
RT   the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase.";
RL   J. Mol. Biol. 397:617-626(2010).
CC   -!- FUNCTION: Catalyzes the hydrolysis of N-succinyl-L,L-
CC       diaminopimelic acid (SDAP), forming succinate and LL-2,6-
CC       diaminoheptanedioate (DAP), an intermediate involved in the
CC       bacterial biosynthesis of lysine and meso-diaminopimelic acid, an
CC       essential component of bacterial cell walls. It can only hydrolyze
CC       L,L-N-succinyl-diaminopimelic acid (L,L-SDAP) and is inactive
CC       toward D,L-, L,D-, and D,D-SDAP. {ECO:0000269|PubMed:12962500,
CC       ECO:0000269|PubMed:16421726, ECO:0000269|PubMed:18712420}.
CC   -!- CATALYTIC ACTIVITY: N-succinyl-LL-2,6-diaminoheptanedioate + H(2)O
CC       = succinate + LL-2,6-diaminoheptanedioate.
CC       {ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:18712420}.
CC   -!- COFACTOR: Binds 2 Zn(2+) ion per subunit.
CC   -!- COFACTOR: Binds 1 Co(2+) ion per subunit.
CC   -!- ENZYME REGULATION: Competitively inhibited by L,L-DAP, D,L-DAP, 2-
CC       carboxyethylphosphonic acid (CEPA) and 5-mercaptopentanoic acid
CC       (MSPA). Succinate is a poor inhibitor.
CC       {ECO:0000269|PubMed:14640610, ECO:0000269|PubMed:21577314,
CC       ECO:0000269|PubMed:9671518}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.73 mM for zinc ion (at 30 degrees Celsius and at pH 7.5)
CC         {ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:16421726,
CC         ECO:0000269|PubMed:9671518};
CC         KM=0.73 mM for L,L-SDAP (at 30 degrees Celsius and at pH 7.5)
CC         {ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:16421726,
CC         ECO:0000269|PubMed:9671518};
CC         KM=0.99 mM for cobalt ion (at 30 degrees Celsius and at pH 7.5)
CC         {ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:16421726,
CC         ECO:0000269|PubMed:9671518};
CC         KM=1.3 mM for L,L-SDAP (in the presence of Zn(2+) at 25 degrees
CC         Celsius and at pH 7.6) {ECO:0000269|PubMed:12962500,
CC         ECO:0000269|PubMed:16421726, ECO:0000269|PubMed:9671518};
CC         KM=1.6 mM for L,L-SDAP (in the presence of Co(2+) at 25 degrees
CC         Celsius and at pH 7.6) {ECO:0000269|PubMed:12962500,
CC         ECO:0000269|PubMed:16421726, ECO:0000269|PubMed:9671518};
CC         KM=3.2 mM for a mixture of L,L-SDAP and D,D-SDAP (in the
CC         presence of Zn(2+) at 25 degrees Celsius and at pH 7.6)
CC         {ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:16421726,
CC         ECO:0000269|PubMed:9671518};
CC         KM=4.7 mM for a mixture of L,L-SDAP and D,D-SDAP (in the
CC         presence of Co(2+) at 25 degrees Celsius and at pH 7.6)
CC         {ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:16421726,
CC         ECO:0000269|PubMed:9671518};
CC       pH dependence:
CC         Optimum pH is 7.0 in the presence of Zn(2+). The maximal
CC         velocities are independent of pH in the alkaline region but
CC         decrease below pH 7.0. {ECO:0000269|PubMed:12962500,
CC         ECO:0000269|PubMed:16421726, ECO:0000269|PubMed:9671518};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC       pathway; LL-2,6-diaminopimelate from (S)-tetrahydrodipicolinate
CC       (succinylase route): step 3/3.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20138056}.
CC   -!- MASS SPECTROMETRY: Mass=41350; Method=Electrospray; Range=1-377;
CC       Evidence={ECO:0000269|PubMed:9671518};
CC   -!- SIMILARITY: Belongs to the peptidase M20A family. DapE subfamily.
CC       {ECO:0000305}.
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DR   EMBL; L42023; AAC21776.1; -; Genomic_DNA.
DR   PIR; F64048; F64048.
DR   RefSeq; NP_438276.1; NC_000907.1.
DR   PDB; 3IC1; X-ray; 2.30 A; A/B=1-377.
DR   PDB; 3ISZ; X-ray; 2.00 A; A/B=1-377.
DR   PDB; 4H2K; X-ray; 1.84 A; A/B=1-180, A/B=294-377.
DR   PDBsum; 3IC1; -.
DR   PDBsum; 3ISZ; -.
DR   PDBsum; 4H2K; -.
DR   ProteinModelPortal; P44514; -.
DR   SMR; P44514; 3-375.
DR   STRING; 71421.HI0102; -.
DR   BindingDB; P44514; -.
DR   ChEMBL; CHEMBL1075192; -.
DR   MEROPS; M20.010; -.
DR   EnsemblBacteria; AAC21776; AAC21776; HI_0102.
DR   GeneID; 950999; -.
DR   KEGG; hin:HI0102; -.
DR   PATRIC; 20188671; VBIHaeInf48452_0105.
DR   eggNOG; COG0624; -.
DR   KO; K01439; -.
DR   OMA; LNSTIHK; -.
DR   OrthoDB; EOG60651W; -.
DR   PhylomeDB; P44514; -.
DR   BioCyc; MetaCyc:MONOMER-6421; -.
DR   UniPathway; UPA00034; UER00021.
DR   EvolutionaryTrace; P44514; -.
DR   PRO; PR:P44514; -.
DR   GO; GO:0050897; F:cobalt ion binding; IEA:UniProtKB-HAMAP.
DR   GO; GO:0008237; F:metallopeptidase activity; IEA:InterPro.
DR   GO; GO:0009014; F:succinyl-diaminopimelate desuccinylase activity; IEA:UniProtKB-HAMAP.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-HAMAP.
DR   GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-HAMAP.
DR   GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:UniProtKB-HAMAP.
DR   Gene3D; 3.30.70.360; -; 1.
DR   HAMAP; MF_01690; DapE; 1.
DR   InterPro; IPR001261; ArgE/DapE_CS.
DR   InterPro; IPR005941; DapE_proteobac.
DR   InterPro; IPR002933; Peptidase_M20.
DR   InterPro; IPR011650; Peptidase_M20_dimer.
DR   Pfam; PF07687; M20_dimer; 1.
DR   Pfam; PF01546; Peptidase_M20; 1.
DR   SUPFAM; SSF55031; SSF55031; 1.
DR   TIGRFAMs; TIGR01246; dapE_proteo; 1.
DR   PROSITE; PS00758; ARGE_DAPE_CPG2_1; 1.
DR   PROSITE; PS00759; ARGE_DAPE_CPG2_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amino-acid biosynthesis; Cobalt; Complete proteome;
KW   Diaminopimelate biosynthesis; Direct protein sequencing; Hydrolase;
KW   Lysine biosynthesis; Metal-binding; Reference proteome; Zinc.
FT   CHAIN         1    377       Succinyl-diaminopimelate desuccinylase.
FT                                /FTId=PRO_0000185262.
FT   ACT_SITE     69     69       {ECO:0000305|PubMed:20138056}.
FT   ACT_SITE    134    134       Proton acceptor.
FT                                {ECO:0000269|PubMed:20138056}.
FT   METAL        67     67       Cobalt or zinc 1.
FT   METAL       100    100       Cobalt or zinc 1.
FT   METAL       100    100       Cobalt or zinc 2.
FT   METAL       135    135       Cobalt or zinc 2.
FT   METAL       163    163       Cobalt or zinc 1.
FT   METAL       349    349       Cobalt or zinc 2.
FT   MUTAGEN      67     67       H->A: Reduction of affinity for L,L-SDAP
FT                                and of catalytic efficiency.
FT                                {ECO:0000269|PubMed:18712420}.
FT   MUTAGEN     134    134       E->A: Absence of desuccinylase activity.
FT                                {ECO:0000269|PubMed:16421726}.
FT   MUTAGEN     134    134       E->D: Reduction of the catalytic
FT                                efficiency.
FT                                {ECO:0000269|PubMed:16421726}.
FT   MUTAGEN     349    349       H->A: Absence of desuccinylase activity
FT                                and of zinc ion.
FT                                {ECO:0000269|PubMed:18712420}.
FT   HELIX         1     13
FT   HELIX        25     34
FT   TURN         35     37
FT   STRAND       39     42
FT   STRAND       50     55
FT   STRAND       57     59
FT   STRAND       61     67
FT   HELIX        76     78
FT   TURN         83     85
FT   STRAND       92     95
FT   TURN         96    101
FT   HELIX       102    118
FT   STRAND      123    132
FT   STRAND      134    136
FT   STRAND      139    141
FT   HELIX       142    151
FT   STRAND      158    161
FT   STRAND      166    169
FT   STRAND      172    175
FT   STRAND      180    189
FT   HELIX       200    202
FT   HELIX       204    217
FT   STRAND      225    227
FT   STRAND      231    239
FT   STRAND      249    259
FT   HELIX       265    278
FT   STRAND      283    289
FT   HELIX       300    313
FT   STRAND      318    320
FT   HELIX       326    332
FT   TURN        333    335
FT   STRAND      337    340
FT   TURN        346    349
FT   STRAND      354    356
FT   HELIX       357    374
SQ   SEQUENCE   377 AA;  41353 MW;  C852C7550FFD40C2 CRC64;
     MKEKVVSLAQ DLIRRPSISP NDEGCQQIIA ERLEKLGFQI EWMPFNDTLN LWAKHGTSEP
     VIAFAGHTDV VPTGDENQWS SPPFSAEIID GMLYGRGAAD MKGSLAAMIV AAEEYVKANP
     NHKGTIALLI TSDEEATAKD GTIHVVETLM ARDEKITYCM VGEPSSAKNL GDVVKNGRRG
     SITGNLYIQG IQGHVAYPHL AENPIHKAAL FLQELTTYQW DKGNEFFPPT SLQIANIHAG
     TGSNNVIPAE LYIQFNLRYC TEVTDEIIKQ KVAEMLEKHN LKYRIEWNLS GKPFLTKPGK
     LLDSITSAIE ETIGITPKAE TGGGTSDGRF IALMGAEVVE FGPLNSTIHK VNECVSVEDL
     GKCGEIYHKM LVNLLDS
//
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