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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

Manual assertion based on experiment ini

  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)DescriptionActionsGraphical viewLength
Metal bindingi99Zinc5 Publications1
Binding sitei135Substrate1 Publication1
Binding sitei174Substrate3 Publications1
Metal bindingi193Zinc5 Publications1
Binding sitei196Substrate3 Publications1
Binding sitei201Substrate; via amide nitrogen3 Publications1
Metal bindingi231Zinc; via tele nitrogen5 Publications1

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)DescriptionActionsGraphical viewLength
Mutagenesisi93N → 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 Publication1
Mutagenesisi192N → 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 Publications1

Chemistry databases

ChEMBLiCHEMBL1169593.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001694128 – 254Metallo-beta-lactamase type 2Add BLAST227

Expressioni

Inductioni

By either cefoxitin or imipenem.1 Publication

Interactioni

Subunit structurei

Monomer.3 Publications

Protein-protein interaction databases

STRINGi380703.AHA_0740.

Chemistry databases

BindingDBiP26918.

Structurei

Secondary structure

1254
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi30 – 36Combined sources7
Beta strandi39 – 44Combined sources6
Beta strandi46 – 48Combined sources3
Beta strandi50 – 56Combined sources7
Beta strandi61 – 65Combined sources5
Helixi70 – 81Combined sources12
Beta strandi88 – 92Combined sources5
Beta strandi94 – 97Combined sources4
Helixi98 – 101Combined sources4
Helixi104 – 109Combined sources6
Beta strandi113 – 117Combined sources5
Helixi118 – 138Combined sources21
Beta strandi151 – 156Combined sources6
Beta strandi158 – 160Combined sources3
Turni161 – 164Combined sources4
Beta strandi165 – 168Combined sources4
Beta strandi173 – 177Combined sources5
Beta strandi180 – 183Combined sources4
Turni184 – 187Combined sources4
Beta strandi188 – 190Combined sources3
Helixi192 – 194Combined sources3
Beta strandi198 – 200Combined sources3
Helixi209 – 219Combined sources11
Beta strandi225 – 228Combined sources4
Beta strandi230 – 232Combined sources3
Helixi239 – 250Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
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.
RefSeqiWP_063844282.1. NG_047667.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57102 Genomic DNA. Translation: CAA40386.1.
PIRiS17287.
RefSeqiWP_063844282.1. NG_047667.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi380703.AHA_0740.

Chemistry databases

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...

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: November 2, 2016
This is version 98 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.