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 27-MAR-2024, entry version 146. 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; Bacillota; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 CDD; cd16304; BcII-like_MBL-B1; 1. DR Gene3D; 3.60.15.10; Ribonuclease Z/Hydroxyacylglutathione hydrolase-like; 1. DR InterPro; IPR047917; BcII-like_MBL-B1. DR InterPro; IPR001018; Beta-lactamase_class-B_CS. DR InterPro; IPR001279; Metallo-B-lactamas. DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro. DR PANTHER; PTHR42951:SF20; BETA LACTAMASE; 1. DR PANTHER; PTHR42951; METALLO-BETA-LACTAMASE DOMAIN-CONTAINING; 1. DR Pfam; PF00753; Lactamase_B; 1. DR SMART; SM00849; Lactamase_B; 1. DR SUPFAM; SSF56281; Metallo-hydrolase/oxidoreductase; 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 //