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-MAY-2013, entry version 91.
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.
CC -!- CATALYTIC ACTIVITY: N-succinyl-LL-2,6-diaminoheptanedioate + H(2)O
CC = succinate + LL-2,6-diaminoheptanedioate.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.73 mM for zinc ion (at 30 degrees Celsius and at pH 7.5);
CC KM=0.73 mM for L,L-SDAP (at 30 degrees Celsius and at pH 7.5);
CC KM=0.99 mM for cobalt ion (at 30 degrees Celsius and at pH 7.5);
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);
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);
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 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 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;
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.
CC -!- MASS SPECTROMETRY: Mass=41350; Method=Electrospray; Range=1-377;
CC Source=PubMed:9671518;
CC -!- SIMILARITY: Belongs to the peptidase M20A family. DapE subfamily.
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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=1-377.
DR PDBsum; 3IC1; -.
DR PDBsum; 3ISZ; -.
DR PDBsum; 4H2K; -.
DR ProteinModelPortal; P44514; -.
DR SMR; P44514; 3-375.
DR STRING; 71421.HI0102; -.
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; MWARRGN; -.
DR ProtClustDB; PRK13009; -.
DR BioCyc; MetaCyc:MONOMER-6421; -.
DR UniPathway; UPA00034; UER00021.
DR BindingDB; P44514; -.
DR ChEMBL; CHEMBL1075192; -.
DR EvolutionaryTrace; P44514; -.
DR GO; GO:0050897; F:cobalt ion binding; IEA:HAMAP.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:InterPro.
DR GO; GO:0009014; F:succinyl-diaminopimelate desuccinylase activity; IEA:HAMAP.
DR GO; GO:0008270; F:zinc ion binding; IEA:HAMAP.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:HAMAP.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:HAMAP.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
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; Peptidase_M20_dimer; 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 Probable.
FT ACT_SITE 134 134 Proton acceptor.
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 MUTAGEN 134 134 E->A: Absence of desuccinylase activity.
FT MUTAGEN 134 134 E->D: Reduction of the catalytic
FT efficiency.
FT MUTAGEN 349 349 H->A: Absence of desuccinylase activity
FT and of zinc ion.
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
//
