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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   26-NOV-2014, entry version 103.
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   REACTION 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:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 2 Zn(2+) ion per subunit.;
CC   -!- COFACTOR:
CC       Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC       Note=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   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       {ECO:0000244|PDB:4H2K}.
FT   HELIX        25     34       {ECO:0000244|PDB:4H2K}.
FT   TURN         35     37       {ECO:0000244|PDB:4H2K}.
FT   STRAND       39     42       {ECO:0000244|PDB:4H2K}.
FT   STRAND       50     55       {ECO:0000244|PDB:4H2K}.
FT   STRAND       57     59       {ECO:0000244|PDB:4H2K}.
FT   STRAND       61     67       {ECO:0000244|PDB:4H2K}.
FT   HELIX        76     78       {ECO:0000244|PDB:4H2K}.
FT   TURN         83     85       {ECO:0000244|PDB:3IC1}.
FT   STRAND       92     95       {ECO:0000244|PDB:4H2K}.
FT   TURN         96    101       {ECO:0000244|PDB:4H2K}.
FT   HELIX       102    118       {ECO:0000244|PDB:4H2K}.
FT   STRAND      123    132       {ECO:0000244|PDB:4H2K}.
FT   STRAND      134    136       {ECO:0000244|PDB:4H2K}.
FT   STRAND      139    141       {ECO:0000244|PDB:3ISZ}.
FT   HELIX       142    151       {ECO:0000244|PDB:4H2K}.
FT   STRAND      158    161       {ECO:0000244|PDB:4H2K}.
FT   STRAND      166    169       {ECO:0000244|PDB:4H2K}.
FT   STRAND      172    175       {ECO:0000244|PDB:4H2K}.
FT   STRAND      180    189       {ECO:0000244|PDB:3ISZ}.
FT   HELIX       200    202       {ECO:0000244|PDB:3ISZ}.
FT   HELIX       204    217       {ECO:0000244|PDB:3ISZ}.
FT   STRAND      225    227       {ECO:0000244|PDB:3ISZ}.
FT   STRAND      231    239       {ECO:0000244|PDB:3ISZ}.
FT   STRAND      249    259       {ECO:0000244|PDB:3ISZ}.
FT   HELIX       265    278       {ECO:0000244|PDB:3ISZ}.
FT   STRAND      283    289       {ECO:0000244|PDB:3ISZ}.
FT   HELIX       300    313       {ECO:0000244|PDB:4H2K}.
FT   STRAND      318    320       {ECO:0000244|PDB:4H2K}.
FT   HELIX       326    332       {ECO:0000244|PDB:4H2K}.
FT   TURN        333    335       {ECO:0000244|PDB:4H2K}.
FT   STRAND      337    340       {ECO:0000244|PDB:4H2K}.
FT   TURN        346    349       {ECO:0000244|PDB:4H2K}.
FT   STRAND      354    356       {ECO:0000244|PDB:4H2K}.
FT   HELIX       357    374       {ECO:0000244|PDB:4H2K}.
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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