BLAB_SERMA
ID BLAB_SERMA Reviewed; 246 AA.
AC P52699;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Metallo-beta-lactamase type 2 {ECO:0000305};
DE EC=3.5.2.6 {ECO:0000269|PubMed:8141584};
DE AltName: Full=B2 metallo-beta-lactamase {ECO:0000305};
DE AltName: Full=BLA-IMP {ECO:0000303|PubMed:8141584};
DE Short=IMP-1 {ECO:0000303|PubMed:8141584};
DE AltName: Full=Beta-lactamase type II {ECO:0000303|PubMed:8141584};
DE AltName: Full=Metallo-beta-lactamase type II {ECO:0000303|PubMed:8141584};
DE Flags: Precursor;
OS Serratia marcescens.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Yersiniaceae; Serratia.
OX NCBI_TaxID=615;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 19-42, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND
RP SUBSTRATE SPECIFICITY.
RC STRAIN=AK9373 / TN9106;
RX PubMed=8141584; DOI=10.1128/aac.38.1.71;
RA Osano E., Arakawa Y., Wacharotayankun R., Ohta M., Horii T., Ito H.,
RA Yoshimura F., Kato N.;
RT "Molecular characterization of an enterobacterial metallo beta-lactamase
RT found in a clinical isolate of Serratia marcescens that shows imipenem
RT resistance.";
RL Antimicrob. Agents Chemother. 38:71-78(1994).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 19-246 IN COMPLEX WITH SUBSTRATE
RP ANALOG 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. {ECO:0000269|PubMed:8141584}.
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:8141584};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:26482303};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:26482303};
CC -!- ACTIVITY REGULATION: Inhibited by captopril stereoisomers, Hg(2+),
CC Fe(2+), Cu(2+) and by chelating agents such as EDTA (PubMed:8141584,
CC PubMed:26482303). This enzyme is not susceptible to inactivation by the
CC beta-lactamase-blocking agents clavulanic acid or cloxacillin
CC (PubMed:8141584). {ECO:0000269|PubMed:26482303,
CC ECO:0000269|PubMed:8141584}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.74 uM for meropenem {ECO:0000269|PubMed:8141584};
CC KM=1.24 uM for ceftazidime {ECO:0000269|PubMed:8141584};
CC KM=2.07 uM for ceftizoxime and panipenem
CC {ECO:0000269|PubMed:8141584};
CC KM=2.13 uM for cefoperazone {ECO:0000269|PubMed:8141584};
CC KM=2.15 uM for ampicillin {ECO:0000269|PubMed:8141584};
CC KM=3.97 uM for aztreonam {ECO:0000269|PubMed:8141584};
CC KM=7.33 uM for imipenem {ECO:0000269|PubMed:8141584};
CC KM=7.55 uM for moxalactam {ECO:0000269|PubMed:8141584};
CC KM=7.74 uM for cephaloridine {ECO:0000269|PubMed:8141584};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P25910}.
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; S71932; AAB30289.1; -; Genomic_DNA.
DR EMBL; D50438; BAA08930.1; -; Genomic_DNA.
DR RefSeq; WP_003159548.1; NG_049172.1.
DR PDB; 1DD6; X-ray; 2.00 A; A/B=19-246.
DR PDB; 1VGN; X-ray; 2.63 A; A/B=19-246.
DR PDB; 1WUO; X-ray; 2.01 A; A/B/C/D=19-246.
DR PDB; 1WUP; X-ray; 3.00 A; A/B/C/D=19-246.
DR PDB; 2DOO; X-ray; 2.43 A; A/B=19-246.
DR PDB; 4C1F; X-ray; 2.01 A; A/B=19-246.
DR PDB; 4C1G; X-ray; 1.71 A; A/B=19-246.
DR PDB; 5EV6; X-ray; 1.98 A; A/B/C/D=19-246.
DR PDB; 5EV8; X-ray; 2.30 A; A/B/C/D=19-246.
DR PDB; 5EWA; X-ray; 2.30 A; A/B/C/D=19-246.
DR PDB; 5HH4; X-ray; 2.00 A; A/B/C/D=19-246.
DR PDB; 5Y5B; X-ray; 1.70 A; A=19-246.
DR PDB; 6JED; X-ray; 1.57 A; A=19-246.
DR PDB; 6JKA; X-ray; 2.01 A; A/B/C/D=20-242.
DR PDB; 6LBL; X-ray; 1.68 A; A=19-246.
DR PDB; 6ZYR; X-ray; 1.87 A; A/B/C/D=19-246.
DR PDB; 6ZYS; X-ray; 1.87 A; A/B/C/D=19-246.
DR PDB; 7DTM; X-ray; 2.00 A; A/B/C/D=19-246.
DR PDB; 7DTN; X-ray; 1.85 A; A/B/C/D=19-246.
DR PDBsum; 1DD6; -.
DR PDBsum; 1VGN; -.
DR PDBsum; 1WUO; -.
DR PDBsum; 1WUP; -.
DR PDBsum; 2DOO; -.
DR PDBsum; 4C1F; -.
DR PDBsum; 4C1G; -.
DR PDBsum; 5EV6; -.
DR PDBsum; 5EV8; -.
DR PDBsum; 5EWA; -.
DR PDBsum; 5HH4; -.
DR PDBsum; 5Y5B; -.
DR PDBsum; 6JED; -.
DR PDBsum; 6JKA; -.
DR PDBsum; 6LBL; -.
DR PDBsum; 6ZYR; -.
DR PDBsum; 6ZYS; -.
DR PDBsum; 7DTM; -.
DR PDBsum; 7DTN; -.
DR AlphaFoldDB; P52699; -.
DR BMRB; P52699; -.
DR SMR; P52699; -.
DR BindingDB; P52699; -.
DR ChEMBL; CHEMBL4105964; -.
DR DrugBank; DB02154; 2,3-Bis-Benzo[1,3]Dioxol-5-Ylmethyl-Succinic Acid.
DR DrugBank; DB04749; 2-(3-OXO-PROPYLSULFANYLCARBONYL)-ETHANETHIOLATE.
DR DrugBank; DB02450; 2-Benzo[1,3]Dioxol-5-Ylmethyl-3-Benzyl-Succinic Acid.
DR DrugBank; DB02706; Mercaptocarboxylate Inhibitor.
DR DrugBank; DB07526; N-[4-({[5-(DIMETHYLAMINO)-1-NAPHTHYL]SULFONYL}AMINO)BUTYL]-3-SULFANYLPROPANAMIDE.
DR KEGG; ag:AAB30289; -.
DR BRENDA; 3.5.2.6; 5690.
DR SABIO-RK; P52699; -.
DR EvolutionaryTrace; P52699; -.
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; Direct protein sequencing; Hydrolase;
KW Metal-binding; Periplasm; Signal; Zinc.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:8141584"
FT CHAIN 19..246
FT /note="Metallo-beta-lactamase type 2"
FT /id="PRO_0000016946"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26482303"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26482303"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26482303"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26482303"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26482303"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26482303"
FT BINDING 185
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P25910"
FT BINDING 215
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26482303"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 34..43
FT /evidence="ECO:0007829|PDB:6JED"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 47..58
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:6JED"
FT HELIX 71..83
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 87..92
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:6JED"
FT HELIX 98..101
FT /evidence="ECO:0007829|PDB:6JED"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:6JED"
FT HELIX 118..126
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:6JED"
FT TURN 145..147
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:6JED"
FT TURN 167..170
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:6JED"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:6JED"
FT HELIX 194..204
FT /evidence="ECO:0007829|PDB:6JED"
FT STRAND 209..216
FT /evidence="ECO:0007829|PDB:6JED"
FT HELIX 222..238
FT /evidence="ECO:0007829|PDB:6JED"
SQ SEQUENCE 246 AA; 27120 MW; 9B2599E8F1B22D36 CRC64;
MSKLSVFFIF LFCSIATAAE SLPDLKIEKL DEGVYVHTSF EEVNGWGVVP KHGLVVLVNA
EAYLIDTPFT AKDTEKLVTW FVERGYKIKG SISSHFHSDS TGGIEWLNSR SIPTYASELT
NELLKKDGKV QATNSFSGVN YWLVKNKIEV FYPGPGHTPD NVVVWLPERK ILFGGCFIKP
YGLGNLGDAN IEAWPKSAKL LKSKYGKAKL VVPSHSEVGD ASLLKLTLEQ AVKGLNESKK
PSKPSN
