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Protein

Metallo-beta-lactamase type 2

Gene

cphA

Organism
Aeromonas hydrophila
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Confers resistance to the different beta-lactams antibiotics (penicillin, cephalosporin and carbapenem) via the hydrolysis of the beta-lactam ring (PubMed:15588826, PubMed:17307979, PubMed:1856163, PubMed:19651913, PubMed:2327760). It is able to hydrolyze penicillin and imipenem, but is much less active against cephalothin, cefotaxime, meropenem and ceftazidime (PubMed:1856163, PubMed:2327760).5 Publications

Catalytic activityi

A beta-lactam + H2O = a substituted beta-amino acid.4 Publications

Cofactori

Zn2+5 PublicationsNote: Binds 1 Zn2+ ions per subunit.5 Publications

Enzyme regulationi

Competitively inhibited by mercaptophosphonate and pyridine carboxylate derivatives (PubMed:17307979, PubMed:20527888). Also inhibited by the binding of a second zinc ion and by chelating agents such as EDTA (PubMed:1856163, PubMed:2327760, PubMed:19651913).5 Publications

Kineticsi

Kcat is 1200 sec(-1) for lactamase activity with imipenem as substrate (PubMed:15588826, PubMed:19651913). Kcat is 300 sec(-1) for lactamase activity with biapenem as substrate (PubMed:15588826). Kcat is 210 sec(-1) for lactamase activity with imipenem as substrate (at pH 7) (PubMed:17307979). Kcat is 140 sec(-1) for lactamase activity with imipenem as substrate (at pH 8) (PubMed:17307979). Kcat is 49 sec(-1) for lactamase activity with imipenem as substrate (at pH 9) (PubMed:17307979). Kcat is 0.008 sec(-1) for lactamase activity with nitrocefin as substrate (PubMed:19651913).3 Publications

  1. KM=0.8 µM for cefuroxime1 Publication
  2. KM=9 µM for ceftazidime1 Publication
  3. KM=15 µM for cefotaxime1 Publication
  4. KM=19 µM for cloxacillin1 Publication
  5. KM=28 µM for cephalothin1 Publication
  6. KM=30 µM for imipenem1 Publication
  7. KM=30.6 µM for nitrocefin1 Publication
  8. KM=53.3 µM for aztreonam1 Publication
  9. KM=63 µM for imipenem (at pH 9)1 Publication
  10. KM=83 µM for imipenem (at pH 8)1 Publication
  11. KM=120 µM for imipenem (at pH 7)1 Publication
  12. KM=124 µM for penicillin G1 Publication
  13. KM=166 µM for biapenem1 Publication
  14. KM=340 µM for imipenem2 Publications
  15. KM=1300 µM for nitrocefin2 Publications
  1. Vmax=170 µmol/min/mg enzyme with penicillin G as substrate1 Publication
  2. Vmax=100 µmol/min/mg enzyme with nitrocefin as substrate1 Publication
  3. Vmax=68.5 µmol/min/mg enzyme with imipenem as substrate1 Publication
  4. Vmax=12.8 µmol/min/mg enzyme with cefuroxime as substrate1 Publication
  5. Vmax=3.2 µmol/min/mg enzyme with aztreonam as substrate1 Publication
  6. Vmax=1.8 µmol/min/mg enzyme with cephalothin as substrate1 Publication
  7. Vmax=1.1 µmol/min/mg enzyme with cloxacillin as substrate1 Publication
  8. Vmax=0.5 µmol/min/mg enzyme with cefotaxime as substrate1 Publication
  9. Vmax=0.3 µmol/min/mg enzyme with ceftazidime as substrate1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi99 – 991Zinc5 Publications
Binding sitei135 – 1351Substrate1 Publication
Binding sitei174 – 1741Substrate3 Publications
Metal bindingi193 – 1931Zinc5 Publications
Binding sitei196 – 1961Substrate3 Publications
Binding sitei201 – 2011Substrate; via amide nitrogen3 Publications
Metal bindingi231 – 2311Zinc; via tele nitrogen5 Publications

GO - Molecular functioni

  • beta-lactamase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • antibiotic catabolic process Source: UniProtKB
  • response to antibiotic Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Antibiotic resistance

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.5.2.6. 164.
SABIO-RKP26918.

Names & Taxonomyi

Protein namesi
Recommended name:
Metallo-beta-lactamase type 2Curated (EC:3.5.2.64 Publications)
Alternative name(s):
B2 metallo-beta-lactamaseCurated
Beta-lactamase II1 Publication
Carbapenem-hydrolyzing metallo-beta-lactamase1 Publication
Metallo-beta-lactamase type II1 Publication
Gene namesi
Name:cphA1 Publication
OrganismiAeromonas hydrophila
Taxonomic identifieri644 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaAeromonadalesAeromonadaceaeAeromonas

Subcellular locationi

  • Periplasm 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Periplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi93 – 931N → H: Behaves as B1 and B3 enzymes, which are more inhibited by 2-picolinic acid than by 2,4-PDCA; when associated with G-192. 1 Publication
Mutagenesisi192 – 1921N → G: Slight decrease of the catalytic efficiency and slight increase of the affinity for both biapenem and imipenem. Behaves as B1 and B3 enzymes, which are more inhibited by 2-picolinic acid than by 2,4-PDCA; when associated with H-93. 3 Publications

Chemistry

ChEMBLiCHEMBL1169593.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Chaini28 – 254227Metallo-beta-lactamase type 2PRO_0000016941Add
BLAST

Expressioni

Inductioni

By either cefoxitin or imipenem.1 Publication

Interactioni

Subunit structurei

Monomer.3 Publications

Protein-protein interaction databases

STRINGi380703.AHA_0740.

Chemistry

BindingDBiP26918.

Structurei

Secondary structure

1
254
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi30 – 367Combined sources
Beta strandi39 – 446Combined sources
Beta strandi46 – 483Combined sources
Beta strandi50 – 567Combined sources
Beta strandi61 – 655Combined sources
Helixi70 – 8112Combined sources
Beta strandi88 – 925Combined sources
Beta strandi94 – 974Combined sources
Helixi98 – 1014Combined sources
Helixi104 – 1096Combined sources
Beta strandi113 – 1175Combined sources
Helixi118 – 13821Combined sources
Beta strandi151 – 1566Combined sources
Beta strandi158 – 1603Combined sources
Turni161 – 1644Combined sources
Beta strandi165 – 1684Combined sources
Beta strandi173 – 1775Combined sources
Beta strandi180 – 1834Combined sources
Turni184 – 1874Combined sources
Beta strandi188 – 1903Combined sources
Helixi192 – 1943Combined sources
Beta strandi198 – 2003Combined sources
Helixi209 – 21911Combined sources
Beta strandi225 – 2284Combined sources
Beta strandi230 – 2323Combined sources
Helixi239 – 25012Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1X8GX-ray1.70A28-254[»]
1X8HX-ray1.60A28-254[»]
1X8IX-ray1.90A28-254[»]
2GKLX-ray1.86A28-254[»]
2QDSX-ray1.66A28-254[»]
3F9OX-ray2.03A28-254[»]
3FAIX-ray1.70A28-254[»]
3IOFX-ray1.44A28-254[»]
3IOGX-ray1.41A28-254[»]
3SW3X-ray2.35A28-254[»]
3T9MX-ray2.03A28-254[»]
ProteinModelPortaliP26918.
SMRiP26918. Positions 28-251.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26918.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG4107YH7. Bacteria.
ENOG410ZW82. LUCA.

Family and domain databases

Gene3Di3.60.15.10. 1 hit.
InterProiIPR001018. Beta-lactamase_class-B_CS.
IPR001279. Metallo-B-lactamas.
[Graphical view]
PfamiPF00753. Lactamase_B. 1 hit.
[Graphical view]
SMARTiSM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMiSSF56281. SSF56281. 1 hit.
PROSITEiPS00743. BETA_LACTAMASE_B_1. 1 hit.
PS00744. BETA_LACTAMASE_B_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P26918-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMKGWMKCGL AGAVVLMASF WGGSVRAAGM SLTQVSGPVY VVEDNYYVQE
60 70 80 90 100
NSMVYFGAKG VTVVGATWTP DTARELHKLI KRVSRKPVLE VINTNYHTDR
110 120 130 140 150
AGGNAYWKSI GAKVVSTRQT RDLMKSDWAE IVAFTRKGLP EYPDLPLVLP
160 170 180 190 200
NVVHDGDFTL QEGKVRAFYA GPAHTPDGIF VYFPDEQVLY GNCILKEKLG
210 220 230 240 250
NLSFADVKAY PQTLERLKAM KLPIKTVIGG HDSPLHGPEL IDHYEALIKA

APQS
Length:254
Mass (Da):28,016
Last modified:August 1, 1992 - v1
Checksum:i9D54760E17CF4B50
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57102 Genomic DNA. Translation: CAA40386.1.
PIRiS17287.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57102 Genomic DNA. Translation: CAA40386.1.
PIRiS17287.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1X8GX-ray1.70A28-254[»]
1X8HX-ray1.60A28-254[»]
1X8IX-ray1.90A28-254[»]
2GKLX-ray1.86A28-254[»]
2QDSX-ray1.66A28-254[»]
3F9OX-ray2.03A28-254[»]
3FAIX-ray1.70A28-254[»]
3IOFX-ray1.44A28-254[»]
3IOGX-ray1.41A28-254[»]
3SW3X-ray2.35A28-254[»]
3T9MX-ray2.03A28-254[»]
ProteinModelPortaliP26918.
SMRiP26918. Positions 28-251.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi380703.AHA_0740.

Chemistry

BindingDBiP26918.
ChEMBLiCHEMBL1169593.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG4107YH7. Bacteria.
ENOG410ZW82. LUCA.

Enzyme and pathway databases

BRENDAi3.5.2.6. 164.
SABIO-RKP26918.

Miscellaneous databases

EvolutionaryTraceiP26918.

Family and domain databases

Gene3Di3.60.15.10. 1 hit.
InterProiIPR001018. Beta-lactamase_class-B_CS.
IPR001279. Metallo-B-lactamas.
[Graphical view]
PfamiPF00753. Lactamase_B. 1 hit.
[Graphical view]
SMARTiSM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMiSSF56281. SSF56281. 1 hit.
PROSITEiPS00743. BETA_LACTAMASE_B_1. 1 hit.
PS00744. BETA_LACTAMASE_B_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The Aeromonas hydrophila cphA gene: molecular heterogeneity among class B metallo-beta-lactamases."
    Massidda O., Rossolini G.M., Satta G.
    J. Bacteriol. 173:4611-4617(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, ENZYME REGULATION, SUBSTRATE SPECIFICITY, SUBUNIT.
    Strain: AE036.
  2. "Purification and characterization of inducible beta-lactamases in Aeromonas spp."
    Iaconis J.P., Sanders C.C.
    Antimicrob. Agents Chemother. 34:44-51(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, INDUCTION, SUBUNIT, SUBSTRATE SPECIFICITY.
  3. "A metallo-beta-lactamase enzyme in action: crystal structures of the monozinc carbapenemase CphA and its complex with biapenem."
    Garau G., Bebrone C., Anne C., Galleni M., Frere J.M., Dideberg O.
    J. Mol. Biol. 345:785-795(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 28-254 OF WILD-TYPE AND MUTANT GLY-192 IN COMPLEX WITH SUBSTRATE ANALOGS AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASN-192, COFACTOR, SUBUNIT, REACTION MECHANISM.
  4. "Competitive inhibitors of the CphA metallo-beta-lactamase from Aeromonas hydrophila."
    Horsfall L.E., Garau G., Lienard B.M., Dideberg O., Schofield C.J., Frere J.M., Galleni M.
    Antimicrob. Agents Chemother. 51:2136-2142(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 28-254 IN COMPLEX WITH SUBSTRATE ANALOG AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, MUTAGENESIS OF ASN-93 AND ASN-192, COFACTOR.
  5. Cited for: X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 28-254 IN COMPLEX WITH SUBSTRATE ANALOG AND ZINC IONS, COFACTOR.
  6. "The structure of the dizinc subclass B2 metallo-beta-lactamase CphA reveals that the second inhibitory zinc ion binds in the histidine site."
    Bebrone C., Delbruck H., Kupper M.B., Schlomer P., Willmann C., Frere J.M., Fischer R., Galleni M., Hoffmann K.M.
    Antimicrob. Agents Chemother. 53:4464-4471(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 28-254 OF WILD-TYPE AND MUTANT GLY-192 IN COMPLEX WITH SUBSTRATE ANALOGS AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASN-192, ENZYME REGULATION, COFACTOR.
  7. "Mercaptophosphonate compounds as broad-spectrum inhibitors of the metallo-beta-lactamases."
    Lassaux P., Hamel M., Gulea M., Delbruck H., Mercuri P.S., Horsfall L., Dehareng D., Kupper M., Frere J.M., Hoffmann K., Galleni M., Bebrone C.
    J. Med. Chem. 53:4862-4876(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.41 ANGSTROMS) OF 28-254 IN COMPLEX WITH SUBSTRATE ANALOGS AND ZINC IONS, ENZYME REGULATION, COFACTOR.
  8. "Crystal structure of mutant C221D of carbapenemase CphA from Aeromonas hydrophila."
    Delbruck H., Bebrone C., Hoffmann K.M.V., Galleni M.
    Submitted (AUG-2011) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 28-254.

Entry informationi

Entry nameiBLAB_AERHY
AccessioniPrimary (citable) accession number: P26918
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: April 13, 2016
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.