DAPE_HAEIN
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 03-AUG-2022, entry version 141.
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., Weidman J.F.,
RA Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R.,
RA Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D.,
RA Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A.,
RA Small K.V., Fraser C.M., Smith H.O., 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 PROPERTIES,
RP AND ACTIVITY 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 isotope
RT 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 acid
RT desuccinylase from Haemophilus influenzae.";
RL Biochemistry 42:10756-10763(2003).
RN [4]
RP COFACTOR, AND ACTIVITY 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 from
RT 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-altered
RT dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from
RT 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 from
RT Haemophilus influenzae contains two active-site histidine residues.";
RL J. Biol. Inorg. Chem. 14:1-10(2009).
RN [7]
RP ACTIVITY 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 of L-
RT captopril antimicrobial activity.";
RL Bioinorg. Chem. Appl. 2011:306465-306465(2011).
RN [8] {ECO:0007744|PDB:3IC1, ECO:0007744|PDB:3ISZ}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH ZINC IONS, COFACTOR,
RP REACTION 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 the
RT 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-diaminopimelic
CC acid (SDAP), forming succinate and LL-2,6-diaminoheptanedioate (DAP),
CC an intermediate involved in the bacterial biosynthesis of lysine and
CC meso-diaminopimelic acid, an essential component of bacterial cell
CC walls. It can only hydrolyze L,L-N-succinyl-diaminopimelic acid (L,L-
CC SDAP) and is inactive toward D,L-, L,D-, and D,D-SDAP.
CC {ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:16421726,
CC ECO:0000269|PubMed:18712420}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-succinyl-(2S,6S)-2,6-diaminoheptanedioate = (2S,6S)-
CC 2,6-diaminoheptanedioate + succinate; Xref=Rhea:RHEA:22608,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:30031, ChEBI:CHEBI:57609,
CC ChEBI:CHEBI:58087; EC=3.5.1.18;
CC Evidence={ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:18712420};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:20138056};
CC Note=Binds 2 Zn(2+) ion per subunit. {ECO:0000269|PubMed:20138056};
CC -!- ACTIVITY REGULATION: Competitively inhibited by L,L-DAP, D,L-DAP, 2-
CC carboxyethylphosphonic acid (CEPA) and 5-mercaptopentanoic acid (MSPA).
CC Succinate is a poor inhibitor. {ECO:0000269|PubMed:14640610,
CC ECO:0000269|PubMed:21577314, 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 presence of
CC 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 presence of
CC 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 velocities
CC are independent of pH in the alkaline region but decrease below pH
CC 7.0. {ECO:0000269|PubMed:12962500, ECO:0000269|PubMed:16421726,
CC 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;
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 RefSeq; WP_005693818.1; 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 PDB; 5VO3; X-ray; 1.95 A; A=1-376.
DR PDBsum; 3IC1; -.
DR PDBsum; 3ISZ; -.
DR PDBsum; 4H2K; -.
DR PDBsum; 5VO3; -.
DR AlphaFoldDB; P44514; -.
DR SMR; P44514; -.
DR STRING; 71421.HI_0102; -.
DR BindingDB; P44514; -.
DR ChEMBL; CHEMBL1075192; -.
DR DrugCentral; P44514; -.
DR EnsemblBacteria; AAC21776; AAC21776; HI_0102.
DR KEGG; hin:HI_0102; -.
DR PATRIC; fig|71421.8.peg.105; -.
DR eggNOG; COG0624; Bacteria.
DR HOGENOM; CLU_021802_4_0_6; -.
DR OMA; LNSHHDT; -.
DR PhylomeDB; P44514; -.
DR BioCyc; HINF71421:G1GJ1-106-MON; -.
DR BioCyc; MetaCyc:MON-6421; -.
DR BRENDA; 3.5.1.18; 2529.
DR SABIO-RK; P44514; -.
DR UniPathway; UPA00034; UER00021.
DR EvolutionaryTrace; P44514; -.
DR Proteomes; UP000000579; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0050897; F:cobalt ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009014; F:succinyl-diaminopimelate desuccinylase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0043093; P:FtsZ-dependent cytokinesis; IBA:GO_Central.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IBA:GO_Central.
DR HAMAP; MF_01690; DapE; 1.
DR InterPro; IPR001261; ArgE/DapE_CS.
DR InterPro; IPR036264; Bact_exopeptidase_dim_dom.
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;
KW Diaminopimelate biosynthesis; Direct protein sequencing; Hydrolase;
KW Lysine biosynthesis; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..377
FT /note="Succinyl-diaminopimelate desuccinylase"
FT /id="PRO_0000185262"
FT ACT_SITE 69
FT /evidence="ECO:0000305|PubMed:20138056"
FT ACT_SITE 134
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:20138056"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20138056,
FT ECO:0007744|PDB:3IC1, ECO:0007744|PDB:3ISZ,
FT ECO:0007744|PDB:4H2K"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20138056,
FT ECO:0007744|PDB:3IC1, ECO:0007744|PDB:3ISZ,
FT ECO:0007744|PDB:4H2K"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20138056,
FT ECO:0007744|PDB:3IC1, ECO:0007744|PDB:4H2K"
FT BINDING 135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20138056,
FT ECO:0007744|PDB:3IC1, ECO:0007744|PDB:4H2K"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20138056,
FT ECO:0007744|PDB:3IC1, ECO:0007744|PDB:3ISZ,
FT ECO:0007744|PDB:4H2K"
FT BINDING 349
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20138056,
FT ECO:0007744|PDB:3IC1, ECO:0007744|PDB:4H2K"
FT MUTAGEN 67
FT /note="H->A: Reduction of affinity for L,L-SDAP and of
FT catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:18712420"
FT MUTAGEN 134
FT /note="E->A: Absence of desuccinylase activity."
FT /evidence="ECO:0000269|PubMed:16421726"
FT MUTAGEN 134
FT /note="E->D: Reduction of the catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:16421726"
FT MUTAGEN 349
FT /note="H->A: Absence of desuccinylase activity and of zinc
FT ion."
FT /evidence="ECO:0000269|PubMed:18712420"
FT HELIX 1..13
FT /evidence="ECO:0007829|PDB:4H2K"
FT HELIX 25..34
FT /evidence="ECO:0007829|PDB:4H2K"
FT TURN 35..37
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:4H2K"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:5VO3"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:3IC1"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:4H2K"
FT TURN 96..101
FT /evidence="ECO:0007829|PDB:4H2K"
FT HELIX 102..118
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 123..132
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:5VO3"
FT HELIX 142..151
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 180..189
FT /evidence="ECO:0007829|PDB:5VO3"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:5VO3"
FT HELIX 204..217
FT /evidence="ECO:0007829|PDB:5VO3"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:5VO3"
FT STRAND 231..238
FT /evidence="ECO:0007829|PDB:5VO3"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:5VO3"
FT STRAND 249..259
FT /evidence="ECO:0007829|PDB:5VO3"
FT HELIX 265..278
FT /evidence="ECO:0007829|PDB:5VO3"
FT STRAND 283..291
FT /evidence="ECO:0007829|PDB:5VO3"
FT HELIX 300..313
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:4H2K"
FT HELIX 326..332
FT /evidence="ECO:0007829|PDB:4H2K"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 337..340
FT /evidence="ECO:0007829|PDB:4H2K"
FT TURN 346..349
FT /evidence="ECO:0007829|PDB:4H2K"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:4H2K"
FT HELIX 357..374
FT /evidence="ECO:0007829|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
