BLAB_BACFG
ID BLAB_BACFG Reviewed; 249 AA.
AC P25910;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Metallo-beta-lactamase type 2 {ECO:0000305};
DE EC=3.5.2.6 {ECO:0000269|PubMed:9712862};
DE AltName: Full=B2 metallo-beta-lactamase {ECO:0000305};
DE AltName: Full=Beta-lactamase II {ECO:0000303|PubMed:2121094};
DE AltName: Full=Carbapenem and cephamycin resistance {ECO:0000303|PubMed:2121094};
DE Short=CCRA {ECO:0000303|PubMed:2121094};
DE AltName: Full=Cephalosporinase {ECO:0000305};
DE AltName: Full=Imipenem-cefoxitin hydrolyzing enzyme {ECO:0000303|PubMed:2110145};
DE AltName: Full=Metallo-beta-lactamase type II {ECO:0000303|PubMed:2121094};
DE AltName: Full=Penicillinase {ECO:0000305};
DE AltName: Full=Zinc-requiring beta-lactamase {ECO:0000303|PubMed:2121094};
DE Flags: Precursor;
GN Name=ccrA {ECO:0000303|PubMed:2121094};
GN Synonyms=cfiA {ECO:0000303|PubMed:2110145};
OS Bacteroides fragilis.
OC Bacteria; Bacteroidetes; Bacteroidia; Bacteroidales; Bacteroidaceae;
OC Bacteroides.
OX NCBI_TaxID=817;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND ACTIVITY REGULATION.
RC STRAIN=TAL3636;
RX PubMed=2121094; DOI=10.1128/aac.34.8.1590;
RA Rasmussen B.A., Gluzman Y., Tally F.P.;
RT "Cloning and sequencing of the class B beta-lactamase gene (ccrA) from
RT Bacteroides fragilis TAL3636.";
RL Antimicrob. Agents Chemother. 34:1590-1592(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, ACTIVITY REGULATION, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=TAL3636;
RX PubMed=1956298; DOI=10.1111/j.1365-2958.1991.tb01895.x;
RA Rasmussen B.A., Gluzman Y., Tally F.P.;
RT "Escherichia coli chromosomal mutations that permit direct cloning of the
RT Bacteroides fragilis metallo-beta-lactamase gene, ccrA.";
RL Mol. Microbiol. 5:1211-1219(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=TAL2480;
RX PubMed=2110145; DOI=10.1128/jb.172.5.2584-2593.1990;
RA Thompson J.S., Malamy M.H.;
RT "Sequencing the gene for an imipenem-cefoxitin-hydrolyzing enzyme (CfiA)
RT from Bacteroides fragilis TAL2480 reveals strong similarity between CfiA
RT and Bacillus cereus beta-lactamase II.";
RL J. Bacteriol. 172:2584-2593(1990).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND COFACTOR.
RX PubMed=9712862; DOI=10.1074/jbc.273.35.22402;
RA Wang Z., Benkovic S.J.;
RT "Purification, characterization, and kinetic studies of a soluble
RT Bacteroides fragilis metallo-beta-lactamase that provides multiple
RT antibiotic resistance.";
RL J. Biol. Chem. 273:22402-22408(1998).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 18-249 IN COMPLEX WITH ZINC IONS,
RP AND COFACTOR.
RX PubMed=8805566; DOI=10.1016/s0969-2126(96)00089-5;
RA Concha N.O., Rasmussen B.A., Bush K., Herzberg O.;
RT "Crystal structure of the wide-spectrum binuclear zinc beta-lactamase from
RT Bacteroides fragilis.";
RL Structure 4:823-836(1996).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 18-249 IN COMPLEX WITH ZINC IONS,
RP AND COFACTOR.
RX PubMed=9416622; DOI=10.1002/pro.5560061225;
RA Concha N.O., Rasmussen B.A., Bush K., Herzberg O.;
RT "Crystal structures of the cadmium- and mercury-substituted metallo-beta-
RT lactamase from Bacteroides fragilis.";
RL Protein Sci. 6:2671-2676(1997).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 18-249 IN COMPLEX WITH ZINC IONS,
RP COFACTOR, AND SUBUNIT.
RX PubMed=9761816; DOI=10.1107/s090744499700927x;
RA Carfi A., Duee E., Paul-Soto R., Galleni M., Frere J.M., Dideberg O.;
RT "X-ray structure of the ZnII beta-lactamase from Bacteroides fragilis in an
RT orthorhombic crystal form.";
RL Acta Crystallogr. D 54:45-57(1998).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 18-249 IN COMPLEX WITH SUBSTRATE
RP ANALOG AND ZINC IONS, ACTIVITY REGULATION, COFACTOR, AND SUBUNIT.
RX PubMed=9578564; DOI=10.1021/bi9730339;
RA Fitzgerald P.M., Wu J.K., Toney J.H.;
RT "Unanticipated inhibition of the metallo-beta-lactamase from Bacteroides
RT fragilis by 4-morpholineethanesulfonic acid (MES): a crystallographic study
RT at 1.85-A resolution.";
RL Biochemistry 37:6791-6800(1998).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 18-249 IN COMPLEX WITH SUBSTRATE
RP ANALOG AND ZINC IONS, ACTIVITY REGULATION, COFACTOR, AND SUBUNIT.
RX PubMed=9545432; DOI=10.1016/s1074-5521(98)90632-9;
RA Toney J.H., Fitzgerald P.M., Grover-Sharma N., Olson S.H., May W.J.,
RA Sundelof J.G., Vanderwall D.E., Cleary K.A., Grant S.K., Wu J.K.,
RA Kozarich J.W., Pompliano D.L., Hammond G.G.;
RT "Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of
RT Bacteroides fragilis metallo-beta-lactamase.";
RL Chem. Biol. 5:185-196(1998).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 18-249 OF MUTANT SER-181 IN
RP COMPLEX WITH ZINC IONS, COFACTOR, AND MUTAGENESIS OF CYS-181.
RX PubMed=10210203; DOI=10.1110/ps.8.1.249;
RA Li Z., Rasmussen B.A., Herzberg O.;
RT "Structural consequences of the active site substitution Cys181 ==> Ser in
RT metallo-beta-lactamase from Bacteroides fragilis.";
RL Protein Sci. 8:249-252(1999).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 18-249 IN COMPLEX WITH SUBSTRATE
RP ANALOG AND ZINC IONS, ACTIVITY REGULATION, COFACTOR, AND SUBUNIT.
RX PubMed=12019104; DOI=10.1128/aac.46.6.1880-1886.2002;
RA Payne D.J., Hueso-Rodriguez J.A., Boyd H., Concha N.O., Janson C.A.,
RA Gilpin M., Bateson J.H., Cheever C., Niconovich N.L., Pearson S.,
RA Rittenhouse S., Tew D., Diez E., Perez P., De La Fuente J., Rees M.,
RA Rivera-Sagredo A.;
RT "Identification of a series of tricyclic natural products as potent broad-
RT spectrum inhibitors of metallo-beta-lactamases.";
RL Antimicrob. Agents Chemother. 46:1880-1886(2002).
CC -!- FUNCTION: Confers resistance to the different beta-lactams antibiotics
CC (penicillin, cephalosporin and carbapenem) via the hydrolysis of the
CC beta-lactam ring. {ECO:0000269|PubMed:2110145,
CC ECO:0000269|PubMed:2121094, ECO:0000269|PubMed:9712862}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-lactam + H2O = a substituted beta-amino acid;
CC Xref=Rhea:RHEA:20401, ChEBI:CHEBI:15377, ChEBI:CHEBI:35627,
CC ChEBI:CHEBI:140347; EC=3.5.2.6;
CC Evidence={ECO:0000269|PubMed:9712862};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:10210203, ECO:0000269|PubMed:12019104,
CC ECO:0000269|PubMed:8805566, ECO:0000269|PubMed:9416622,
CC ECO:0000269|PubMed:9545432, ECO:0000269|PubMed:9578564,
CC ECO:0000269|PubMed:9712862, ECO:0000269|PubMed:9761816};
CC Note=Binds 2 Zn(2+) ions per subunit. It can also bind Cd(2+) and
CC Co(2+) to a lesser extent (PubMed:9416622).
CC {ECO:0000269|PubMed:12019104, ECO:0000269|PubMed:8805566,
CC ECO:0000269|PubMed:9416622, ECO:0000269|PubMed:9545432,
CC ECO:0000269|PubMed:9578564, ECO:0000269|PubMed:9712862,
CC ECO:0000269|PubMed:9761816};
CC -!- ACTIVITY REGULATION: Competitively inhibited by 4-
CC morpholineethanesulfonic acid (MES), SB236050 and biphenyl tetrazoles
CC (BPTs) (PubMed:9578564, PubMed:9545432, PubMed:12019104). Also
CC inhibited by chelating agents such as EDTA and 1,10-phenanthroline
CC (PubMed:9712862). CcrA is not susceptible to inactivation by the beta-
CC lactamase-blocking agents clavulanic acid or tazobactam
CC (PubMed:2121094, PubMed:2110145). {ECO:0000269|PubMed:12019104,
CC ECO:0000269|PubMed:2110145, ECO:0000269|PubMed:2121094,
CC ECO:0000269|PubMed:9545432, ECO:0000269|PubMed:9578564,
CC ECO:0000269|PubMed:9712862}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.1 uM for nitrocefin (with zinc ions at pH 7 and 25 degrees
CC Celsius) {ECO:0000269|PubMed:9712862};
CC KM=14 uM for nitrocefin (with cobalt ions at pH 7 and 25 degrees
CC Celsius) {ECO:0000269|PubMed:9712862};
CC Note=kcat is 225.7 sec(-1) for lactamase activity with nitrocefin as
CC substrate (with zinc ions at pH 7 and 25 degrees Celsius). kcat is
CC 107.6 sec(-1) for lactamase activity with nitrocefin as substrate
CC (with cobalt ions at pH 7 and 25 degrees Celsius).
CC {ECO:0000269|PubMed:9712862};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12019104,
CC ECO:0000269|PubMed:9545432, ECO:0000269|PubMed:9578564,
CC ECO:0000269|PubMed:9761816}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000269|PubMed:2110145}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. Class-B
CC beta-lactamase family. {ECO:0000305}.
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DR EMBL; M63556; AAA22904.1; -; Genomic_DNA.
DR EMBL; M34831; AAA22907.1; -; Genomic_DNA.
DR PIR; A44999; A35263.
DR RefSeq; WP_005808062.1; NZ_QSUS01000007.1.
DR PDB; 1A7T; X-ray; 1.85 A; A/B=18-249.
DR PDB; 1A8T; X-ray; 2.55 A; A/B=18-249.
DR PDB; 1HLK; X-ray; 2.50 A; A/B=21-247.
DR PDB; 1KR3; X-ray; 2.50 A; A/B=18-249.
DR PDB; 1ZNB; X-ray; 1.85 A; A/B=18-249.
DR PDB; 2BMI; X-ray; 2.00 A; A/B=18-249.
DR PDB; 2ZNB; X-ray; 2.15 A; A/B=18-249.
DR PDB; 3ZNB; X-ray; 2.70 A; A/B=18-249.
DR PDB; 4ZNB; X-ray; 2.65 A; A/B=18-249.
DR PDBsum; 1A7T; -.
DR PDBsum; 1A8T; -.
DR PDBsum; 1HLK; -.
DR PDBsum; 1KR3; -.
DR PDBsum; 1ZNB; -.
DR PDBsum; 2BMI; -.
DR PDBsum; 2ZNB; -.
DR PDBsum; 3ZNB; -.
DR PDBsum; 4ZNB; -.
DR AlphaFoldDB; P25910; -.
DR BMRB; P25910; -.
DR SMR; P25910; -.
DR BindingDB; P25910; -.
DR ChEMBL; CHEMBL4840; -.
DR DrugBank; DB02593; 7,8-Dihydroxy-1-Methoxy-3-Methyl-10-Oxo-4,10-Dihydro-1h,3h-Pyrano[4,3-B]Chromene-9-Carboxylic Acid.
DR BRENDA; 3.5.2.6; 755.
DR SABIO-RK; P25910; -.
DR EvolutionaryTrace; P25910; -.
DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell.
DR GO; GO:0008800; F:beta-lactamase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0017001; P:antibiotic catabolic process; IDA:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001018; Beta-lactamase_class-B_CS.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
DR PROSITE; PS00743; BETA_LACTAMASE_B_1; 1.
DR PROSITE; PS00744; BETA_LACTAMASE_B_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Hydrolase; Metal-binding; Periplasm;
KW Signal; Zinc.
FT SIGNAL 1..18
FT /evidence="ECO:0000255, ECO:0000305|PubMed:2110145,
FT ECO:0000305|PubMed:2121094"
FT CHAIN 19..249
FT /note="Metallo-beta-lactamase type 2"
FT /id="PRO_0000016945"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10210203,
FT ECO:0000269|PubMed:12019104, ECO:0000269|PubMed:8805566,
FT ECO:0000269|PubMed:9416622, ECO:0000269|PubMed:9545432,
FT ECO:0000269|PubMed:9578564, ECO:0000269|PubMed:9761816"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10210203,
FT ECO:0000269|PubMed:12019104, ECO:0000269|PubMed:8805566,
FT ECO:0000269|PubMed:9416622, ECO:0000269|PubMed:9545432,
FT ECO:0000269|PubMed:9578564, ECO:0000269|PubMed:9761816"
FT BINDING 103
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12019104,
FT ECO:0000269|PubMed:8805566, ECO:0000269|PubMed:9416622,
FT ECO:0000269|PubMed:9545432, ECO:0000269|PubMed:9578564,
FT ECO:0000269|PubMed:9761816"
FT BINDING 162
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10210203,
FT ECO:0000269|PubMed:12019104, ECO:0000269|PubMed:8805566,
FT ECO:0000269|PubMed:9416622, ECO:0000269|PubMed:9545432,
FT ECO:0000269|PubMed:9578564, ECO:0000269|PubMed:9761816"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12019104,
FT ECO:0000269|PubMed:8805566, ECO:0000269|PubMed:9416622,
FT ECO:0000269|PubMed:9545432, ECO:0000269|PubMed:9578564,
FT ECO:0000269|PubMed:9761816"
FT BINDING 184
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:9545432"
FT BINDING 193
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12019104,
FT ECO:0000269|PubMed:9545432, ECO:0000269|PubMed:9578564"
FT BINDING 223
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12019104,
FT ECO:0000269|PubMed:8805566, ECO:0000269|PubMed:9416622,
FT ECO:0000269|PubMed:9545432, ECO:0000269|PubMed:9578564,
FT ECO:0000269|PubMed:9761816"
FT MUTAGEN 181
FT /note="C->S: The overall structure of the mutant is the
FT same as that of the wild-type, however the site of the
FT second zinc ion is unoccupied."
FT /evidence="ECO:0000269|PubMed:10210203"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:1ZNB"
FT STRAND 25..32
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 34..46
FT /evidence="ECO:0007829|PDB:1A7T"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 50..61
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:1A7T"
FT HELIX 74..88
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:1A7T"
FT HELIX 102..105
FT /evidence="ECO:0007829|PDB:1A7T"
FT HELIX 108..113
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:1A7T"
FT HELIX 122..131
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 137..148
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 151..156
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:1A7T"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:1A7T"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:1A7T"
FT HELIX 202..212
FT /evidence="ECO:0007829|PDB:1A7T"
FT STRAND 217..224
FT /evidence="ECO:0007829|PDB:1A7T"
FT HELIX 230..246
FT /evidence="ECO:0007829|PDB:1A7T"
SQ SEQUENCE 249 AA; 27257 MW; 972B5A594DF5D40D CRC64;
MKTVFILISM LFPVAVMAQK SVKISDDISI TQLSDKVYTY VSLAEIEGWG MVPSNGMIVI
NNHQAALLDT PINDAQTEML VNWVTDSLHA KVTTFIPNHW HGDCIGGLGY LQRKGVQSYA
NQMTIDLAKE KGLPVPEHGF TDSLTVSLDG MPLQCYYLGG GHATDNIVVW LPTENILFGG
CMLKDNQATS IGNISDADVT AWPKTLDKVK AKFPSARYVV PGHGDYGGTE LIEHTKQIVN
QYIESTSKP
