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MetaCyc Enzyme: PSE-4 β-lactamase

Gene: blaP1a Accession Number: G-10219 (MetaCyc)

Species: Pseudomonas aeruginosa

Summary:
Bacterial β-lactamse enzymes hydrolyze the peptide bond in the β-lactam ring of β-lactam antibiotics, providing a mechanism of antibiotic resistance. Antibiotic resistant bacteria remain a major world health problem. Bacterial resistance to β-lactam antibiotics can also involve alterations in penicillin binding proteins and reduced antibiotic permeation across the membrane. The problem is further compounded by β-lactamase gene transfer among bacterial species and the development of resistance to β-lactamase inhibitors such as clavulanate.

Hundreds of bacterial β-lactamase enzymes have been characterized functionally and structurally using both experimental and computational methods, and many crystal structures have been determined. These enzymes have been classified into different groups, subgroups and classes. The nomenclature of individual enzymes, however, remains without convention [Garau05], [Jacoby06] and reviewed in [Majiduddin02].

β-Lactamase classes A, B, C and D are based on amino acid sequence similarity and catalytic mechanism. Class A, C and D enzymes contain an active site serine. Class B enzymes are metallo-β-lactamases, requiring primarily Zn2+ for catalysis. Genes encoding class D enzymes are found predominantly on plasmids (reviewed in [Majiduddin02]). Some examples are class A (this enzyme) , class B carbapenemase and class C β-lactamase; penicillin resistance.

PSE-4 β-lactamase is a class A β-lactamase. This class is found in both Gram-positive and Gram-negative bacteria. The structural motifs and catalytic mechanism of class A enzymes have been reviewed [Majiduddin02]. This enzyme from Pseudomonas aeruginosa has been identified [Newsom70] and characterized [Furth75] and its crystal structure has been determined [Lim01].

The apparent molecular mass of the enzyme was determined by gel filtration chromatography [Furth75].

Gene Citations: [Partridge02]

Locations: periplasmic space

Molecular Weight of Polypeptide: 31.406 kD (from nucleotide sequence), 32.0 kD (experimental) [Furth75 ]

Unification Links: Protein Model Portal:Q7BHK2 , SMR:Q7BHK2 , UniProt:Q7BHK2

Relationship Links: Entrez-Nucleotide:PART-OF:AF313471 , InterPro:IN-FAMILY:IPR000871 , InterPro:IN-FAMILY:IPR012338 , InterPro:IN-FAMILY:IPR023650 , PDB:Structure:1g68 , Pfam:IN-FAMILY:PF00144 , Prints:IN-FAMILY:PR00118 , Prosite:IN-FAMILY:PS00146

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Furth75]

Credits:
Created 03-Oct-2007 by Fulcher CA , SRI International


Enzymatic reaction of: PSE-4 β-lactamase

EC Number: 3.5.2.6

a β-lactam[periplasmic space] + H2O[periplasmic space] <=> a substituted β-amino acid[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Alternative Substrates for a β-lactam: phenoxypropylpenicillin [Furth75 ] , cephalothin [Furth75 ] , cephalosporin 87/312 [Furth75 ] , cephalexin [Furth75 ] , cephaloridine [Furth75 ] , cloxacillin [Furth75 ] , dicloxacillin [Furth75 ] , oxacillin [Furth75 ] , penicillin V [Furth75 ] , phenoxyethylpenicillin [Furth75 ] , carbenicillin [Furth75 ] , α-sulfobenzylpenicillin [Furth75 ] , methicillin [Furth75 ] , penicillin G [Furth75 ] , penicillin N [Furth75 ] , cephalosporin-C [Furth75 ]

Summary:
This enzyme hydrolyzes a variety of β-lactam substrates as shown above. In general, penicillins were hydrolyzed more rapidly than cephalosporins and the Km values were lower for penicillins. However, the penicillins oxacillin, cloxacillin and dicloxacillin. were hydrolyzed slowly. It did not hydrolyze 6-epibenzylpenicillin. The hydrolysis of penicillin G was not inhibited by EDTA or p-chloromercuribenzoate. The enzyme showed substrate inhibition with cloxacillin and cephaloridine. penicillin G protected the enzyme against cloxacillin inhibition [Furth75].

The pH optimum was determined using penicillin G as substrate [Furth75].

pH(opt): 8.0 [Furth75]


References

Furth75: Furth AJ (1975). "Purification and properties of a constitutive beta-lactamase from Pseudomonas aeruginosa strain Dalgleish." Biochim Biophys Acta 377(2);431-43. PMID: 235307

Garau05: Garau G, Di Guilmi AM, Hall BG (2005). "Structure-based phylogeny of the metallo-beta-lactamases." Antimicrob Agents Chemother 49(7);2778-84. PMID: 15980349

Jacoby06: Jacoby GA (2006). "Beta-lactamase nomenclature." Antimicrob Agents Chemother 50(4);1123-9. PMID: 16569819

Lim01: Lim D, Sanschagrin F, Passmore L, De Castro L, Levesque RC, Strynadka NC (2001). "Insights into the molecular basis for the carbenicillinase activity of PSE-4 beta-lactamase from crystallographic and kinetic studies." Biochemistry 40(2);395-402. PMID: 11148033

Majiduddin02: Majiduddin FK, Materon IC, Palzkill TG (2002). "Molecular analysis of beta-lactamase structure and function." Int J Med Microbiol 292(2);127-37. PMID: 12195735

Newsom70: Newsom SW, Sykes RB, Richmond MH (1970). "Detection of a beta-lactamase markedly active against carbenicillin in a strain of Pseudomonas aeruginosa." J Bacteriol 101(3);1079-80. PMID: 4985588

Partridge02: Partridge SR, Brown HJ, Hall RM (2002). "Characterization and movement of the class 1 integron known as Tn2521 and Tn1405." Antimicrob Agents Chemother 46(5);1288-94. PMID: 11959558


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Nov 24, 2014, biocyc13.