BLA2_BACCE
ID BLA2_BACCE Reviewed; 257 AA.
AC P04190;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-1987, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Metallo-beta-lactamase type 2 {ECO:0000305};
DE EC=3.5.2.6 {ECO:0000250|UniProtKB:P25910};
DE AltName: Full=B2 metallo-beta-lactamase {ECO:0000305};
DE AltName: Full=Beta-lactamase II {ECO:0000303|PubMed:3930467};
DE AltName: Full=Cephalosporinase {ECO:0000303|PubMed:3930467};
DE AltName: Full=Metallo-beta-lactamase type II {ECO:0000303|PubMed:3930467};
DE AltName: Full=Metallothioprotein beta-lactamase II {ECO:0000303|PubMed:3930467};
DE AltName: Full=Penicillinase {ECO:0000303|PubMed:3930467};
DE AltName: Full=Zinc-requiring beta-lactamase II {ECO:0000303|PubMed:3930467};
DE Flags: Precursor;
GN Name=blm {ECO:0000303|PubMed:3930467};
OS Bacillus cereus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus;
OC Bacillus cereus group.
OX NCBI_TaxID=1396;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, ACTIVITY REGULATION, AND
RP SUBSTRATE SPECIFICITY.
RC STRAIN=569/H / NCTC 9945;
RX PubMed=3930467; DOI=10.1128/jb.164.1.223-229.1985;
RA Hussain M., Carlino A., Madonna M.J., Lampen J.O.;
RT "Cloning and sequencing of the metallothioprotein beta-lactamase II gene of
RT Bacillus cereus 569/H in Escherichia coli.";
RL J. Bacteriol. 164:223-229(1985).
RN [2]
RP PROTEIN SEQUENCE OF 31-183; 187-210 AND 214-257.
RC STRAIN=569/H / NCTC 9945;
RX PubMed=3930290; DOI=10.1016/0014-5793(85)81024-3;
RA Ambler R.P., Daniel M., Fleming J., Hermoso J.M., Pang C., Waley S.G.;
RT "The amino acid sequence of the zinc-requiring beta-lactamase II from the
RT bacterium Bacillus cereus 569.";
RL FEBS Lett. 189:207-211(1985).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS), AND SUBUNIT.
RX PubMed=3124808; DOI=10.1042/bj2480181;
RA Sutton B.J., Artymiuk P.J., Cordero-Borboa A.E., Little C., Phillips D.C.,
RA Waley S.G.;
RT "An X-ray-crystallographic study of beta-lactamase II from Bacillus cereus
RT at 0.35-nm resolution.";
RL Biochem. J. 248:181-188(1987).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 37-257 OF WILD-TYPE AND MUTANT
RP CYS-177 IN COMPLEX WITH ZINC IONS, AND COFACTOR.
RX PubMed=7588620; DOI=10.1002/j.1460-2075.1995.tb00174.x;
RA Carfi A., Pares S., Duee E., Galleni M., Duez C., Frere J.-M., Dideberg O.;
RT "The 3-D structure of a zinc metallo-beta-lactamase from Bacillus cereus
RT reveals a new type of protein fold.";
RL EMBO J. 14:4914-4921(1995).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 31-257 IN COMPLEX WITH CADMIUM
RP IONS.
RA Fabiane S.M., Sohi M.K., Sutton B.J.;
RT "Null.";
RL Submitted (SEP-1997) to the PDB data bank.
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 31-257 IN COMPLEX WITH SUBSTRATE
RP ANALOGS AND ZINC IONS, AND COFACTOR.
RX PubMed=9761898; DOI=10.1107/s0907444997010627;
RA Carfi A., Duee E., Galleni M., Frere J.M., Dideberg O.;
RT "1.85 A resolution structure of the zinc (II) beta-lactamase from Bacillus
RT cereus.";
RL Acta Crystallogr. D 54:313-323(1998).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 31-257 IN COMPLEX WITH ZINC IONS,
RP AND COFACTOR.
RX PubMed=20677753; DOI=10.1021/bi100894r;
RA Gonzalez J.M., Buschiazzo A., Vila A.J.;
RT "Evidence of adaptability in metal coordination geometry and active-site
RT loop conformation among B1 metallo-beta-lactamases.";
RL Biochemistry 49:7930-7938(2010).
RN [8]
RP STRUCTURE BY NMR OF 31-257 IN COMPLEX WITH SUBSTRATE ANALOG AND ZINC IONS,
RP AND COFACTOR.
RX PubMed=24059435; DOI=10.1042/bj20131003;
RA Karsisiotis A.I., Damblon C.F., Roberts G.C.;
RT "Solution structures of the Bacillus cereus metallo-beta-lactamase BcII and
RT its complex with the broad spectrum inhibitor R-thiomandelic acid.";
RL Biochem. J. 456:397-407(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF 31-257 IN COMPLEX WITH SUBSTRATE
RP ANALOGS AND ZINC IONS, ACTIVITY REGULATION, AND COFACTOR.
RX PubMed=26482303; DOI=10.1128/aac.01335-15;
RA Brem J., van Berkel S.S., Zollman D., Lee S.Y., Gileadi O., McHugh P.J.,
RA Walsh T.R., McDonough M.A., Schofield C.J.;
RT "Structural basis of metallo-beta-lactamase inhibition by captopril
RT stereoisomers.";
RL Antimicrob. Agents Chemother. 60:142-150(2015).
CC -!- FUNCTION: Confers resistance to the different beta-lactams antibiotics
CC (penicillin, cephalosporin and carbapenem) via the hydrolysis of the
CC beta-lactam ring. Active on cephalosporin and penicillin.
CC {ECO:0000269|PubMed:3930467}.
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:0000250|UniProtKB:P25910};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:20677753, ECO:0000269|PubMed:24059435,
CC ECO:0000269|PubMed:26482303, ECO:0000269|PubMed:7588620,
CC ECO:0000269|PubMed:9761898};
CC Note=Binds 2 Zn(2+) ions per subunit. The enzyme can also function with
CC only 1 Zn(2+) ion (PubMed:9761898). {ECO:0000269|PubMed:20677753,
CC ECO:0000269|PubMed:24059435, ECO:0000269|PubMed:26482303,
CC ECO:0000269|PubMed:7588620, ECO:0000269|PubMed:9761898};
CC -!- ACTIVITY REGULATION: Inhibited by captopril stereoisomers and
CC iodoacetate (PubMed:3930467, PubMed:26482303). Also inhibited by
CC chelating agents such as EDTA (PubMed:3930467).
CC {ECO:0000269|PubMed:26482303, ECO:0000269|PubMed:3930467}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:3124808}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. Class-B
CC beta-lactamase family. {ECO:0000305}.
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DR EMBL; M11189; AAA22276.1; -; Genomic_DNA.
DR PIR; A91806; PNBSU2.
DR RefSeq; WP_000742468.1; NZ_VEIQ01000003.1.
DR PDB; 1BC2; X-ray; 1.90 A; A/B=31-257.
DR PDB; 1BMC; X-ray; 2.50 A; A=37-257.
DR PDB; 1BVT; X-ray; 1.85 A; A=31-257.
DR PDB; 1DXK; X-ray; 1.85 A; A=31-257.
DR PDB; 1MQO; X-ray; 1.35 A; A=31-257.
DR PDB; 2BC2; X-ray; 1.70 A; A/B=31-257.
DR PDB; 2BFK; X-ray; 2.00 A; A/B=31-257.
DR PDB; 2BFL; X-ray; 1.80 A; A/B=31-257.
DR PDB; 2BFZ; X-ray; 2.30 A; A/B=31-257.
DR PDB; 2BG2; X-ray; 2.40 A; A/B=31-257.
DR PDB; 2BG6; X-ray; 2.30 A; A/B=31-257.
DR PDB; 2BG7; X-ray; 2.10 A; A/B=31-257.
DR PDB; 2BG8; X-ray; 2.50 A; A/B=31-257.
DR PDB; 2BGA; X-ray; 2.70 A; A/B=31-257.
DR PDB; 2M5C; NMR; -; A=31-257.
DR PDB; 2M5D; NMR; -; A=31-257.
DR PDB; 2NXA; X-ray; 2.29 A; A=37-257.
DR PDB; 2NYP; X-ray; 1.84 A; A=37-257.
DR PDB; 2NZE; X-ray; 1.80 A; A/B=36-257.
DR PDB; 2NZF; X-ray; 2.28 A; A=37-257.
DR PDB; 2UYX; X-ray; 1.95 A; A=30-257.
DR PDB; 3BC2; X-ray; 1.70 A; A=31-257.
DR PDB; 3FCZ; X-ray; 2.80 A; A/B=36-247.
DR PDB; 3I0V; X-ray; 1.60 A; A=31-257.
DR PDB; 3I11; X-ray; 1.45 A; A=31-257.
DR PDB; 3I13; X-ray; 1.74 A; A=31-257.
DR PDB; 3I14; X-ray; 1.55 A; A=31-257.
DR PDB; 3I15; X-ray; 1.55 A; A=31-257.
DR PDB; 3KNR; X-ray; 1.71 A; A/B/C/D=31-257.
DR PDB; 3KNS; X-ray; 1.58 A; A/B/C/D=31-257.
DR PDB; 4C09; X-ray; 1.20 A; A=31-257.
DR PDB; 4C1C; X-ray; 1.18 A; A=31-257.
DR PDB; 4C1H; X-ray; 1.10 A; A=31-257.
DR PDB; 4NQ4; X-ray; 1.67 A; A=36-257.
DR PDB; 4NQ5; X-ray; 2.29 A; A=36-257.
DR PDB; 4NQ6; X-ray; 1.80 A; A=36-257.
DR PDB; 4TYT; X-ray; 1.80 A; A=31-257.
DR PDB; 5FQA; X-ray; 1.10 A; A=31-257.
DR PDB; 5FQB; X-ray; 1.90 A; A=31-257.
DR PDB; 5JMX; X-ray; 1.44 A; A=31-257.
DR PDB; 5W8W; X-ray; 2.25 A; A=36-257.
DR PDB; 6EUM; X-ray; 1.18 A; A=31-257.
DR PDB; 6EWE; X-ray; 1.46 A; A=31-257.
DR PDB; 6F2N; X-ray; 1.15 A; A=31-257.
DR PDBsum; 1BC2; -.
DR PDBsum; 1BMC; -.
DR PDBsum; 1BVT; -.
DR PDBsum; 1DXK; -.
DR PDBsum; 1MQO; -.
DR PDBsum; 2BC2; -.
DR PDBsum; 2BFK; -.
DR PDBsum; 2BFL; -.
DR PDBsum; 2BFZ; -.
DR PDBsum; 2BG2; -.
DR PDBsum; 2BG6; -.
DR PDBsum; 2BG7; -.
DR PDBsum; 2BG8; -.
DR PDBsum; 2BGA; -.
DR PDBsum; 2M5C; -.
DR PDBsum; 2M5D; -.
DR PDBsum; 2NXA; -.
DR PDBsum; 2NYP; -.
DR PDBsum; 2NZE; -.
DR PDBsum; 2NZF; -.
DR PDBsum; 2UYX; -.
DR PDBsum; 3BC2; -.
DR PDBsum; 3FCZ; -.
DR PDBsum; 3I0V; -.
DR PDBsum; 3I11; -.
DR PDBsum; 3I13; -.
DR PDBsum; 3I14; -.
DR PDBsum; 3I15; -.
DR PDBsum; 3KNR; -.
DR PDBsum; 3KNS; -.
DR PDBsum; 4C09; -.
DR PDBsum; 4C1C; -.
DR PDBsum; 4C1H; -.
DR PDBsum; 4NQ4; -.
DR PDBsum; 4NQ5; -.
DR PDBsum; 4NQ6; -.
DR PDBsum; 4TYT; -.
DR PDBsum; 5FQA; -.
DR PDBsum; 5FQB; -.
DR PDBsum; 5JMX; -.
DR PDBsum; 5W8W; -.
DR PDBsum; 6EUM; -.
DR PDBsum; 6EWE; -.
DR PDBsum; 6F2N; -.
DR AlphaFoldDB; P04190; -.
DR BMRB; P04190; -.
DR SMR; P04190; -.
DR BindingDB; P04190; -.
DR ChEMBL; CHEMBL4295695; -.
DR DrugBank; DB02153; 3-sulfino-L-alanine.
DR DrugBank; DB01060; Amoxicillin.
DR DrugBank; DB02133; Chlorophyll A.
DR DrugBank; DB04272; Citric acid.
DR ABCD; P04190; 6 sequenced antibodies.
DR BRENDA; 3.5.2.6; 648.
DR SABIO-RK; P04190; -.
DR EvolutionaryTrace; P04190; -.
DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell.
DR GO; GO:0008800; F:beta-lactamase activity; ISS: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 Pfam; PF00753; Lactamase_B; 1.
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; Direct protein sequencing; Hydrolase;
KW Metal-binding; Periplasm; Signal; Zinc.
FT SIGNAL 1..30
FT /evidence="ECO:0000269|PubMed:3930290"
FT CHAIN 31..257
FT /note="Metallo-beta-lactamase type 2"
FT /id="PRO_0000016942"
FT BINDING 116
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20677753,
FT ECO:0000269|PubMed:24059435, ECO:0000269|PubMed:26482303,
FT ECO:0000269|PubMed:7588620, ECO:0000269|PubMed:9761898"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20677753,
FT ECO:0000269|PubMed:24059435, ECO:0000269|PubMed:26482303,
FT ECO:0000269|PubMed:7588620, ECO:0000269|PubMed:9761898"
FT BINDING 120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20677753,
FT ECO:0000269|PubMed:24059435, ECO:0000269|PubMed:26482303"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20677753,
FT ECO:0000269|PubMed:24059435, ECO:0000269|PubMed:26482303,
FT ECO:0000269|PubMed:7588620, ECO:0000269|PubMed:9761898"
FT BINDING 198
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20677753,
FT ECO:0000269|PubMed:24059435, ECO:0000269|PubMed:26482303"
FT BINDING 201
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26482303"
FT BINDING 210
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26482303,
FT ECO:0000269|PubMed:9761898"
FT BINDING 240
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20677753,
FT ECO:0000269|PubMed:24059435, ECO:0000269|PubMed:26482303"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 42..52
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 55..64
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 67..78
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:4C1H"
FT HELIX 91..105
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:4C1H"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:4C1H"
FT HELIX 125..131
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:4C1H"
FT HELIX 139..147
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 159..165
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:4C1H"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2M5C"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:4C1H"
FT HELIX 219..229
FT /evidence="ECO:0007829|PDB:4C1H"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:4C1H"
FT HELIX 247..255
FT /evidence="ECO:0007829|PDB:4C1H"
SQ SEQUENCE 257 AA; 28092 MW; 268EBFB7DDA45431 CRC64;
MKKNTLLKVG LCVGLLGTIQ FVSTISSVQA SQKVEKTVIK NETGTISISQ LNKNVWVHTE
LGSFNGEAVP SNGLVLNTSK GLVLVDSSWD DKLTKELIEM VEKKFQKRVT DVIITHAHAD
RIGGIKTLKE RGIKAHSTAL TAELAKKNGY EEPLGDLQTV TNLKFGNMKV ETFYPGKGHT
EDNIVVWLPQ YNILVGGCLV KSTSAKDLGN VADAYVNEWS TSIENVLKRY RNINAVVPGH
GEVGDKGLLL HTLDLLK
