1HZO

Structure of an extended-spectrum class A beta-lactamase from Proteus vulgaris K1.

(2002) J Mol Biol 317: 109-117

• PubMed: 11916382 Search on PubMed
• DOI: https://doi.org/10.1006/jmbi.2002.5420
• Primary Citation of Related Structures:  
  1HZO


• PubMed Abstract: 
  

  The structure of a chromosomal extended-spectrum beta-lactamase (ESBL) having the ability to hydrolyze cephalosporins including cefuroxime and ceftazidime has been determined by X-ray crystallography to 1.75 A resolution. The species-specific class A beta-lactamase from Proteus vulgaris K1 was crystallized at pH 6.25 and its structure solved by molecular replacement. Refinement of the model resulted in crystallographic R and R(free) of 16.9 % and 19.3 %, respectively. The folding of the K1 enzyme is broadly similar to that of non-ESBL TEM-type beta-lactamases (2 A rmsd for C(alpha)) and differs by only 0.35 A for all atoms of six conserved residues in the catalytic site. Other residues promoting extended-spectrum activity in K1 include the side-chains of atypical residues Ser237 and Lys276. These side-chains are linked by two water molecules, one of which lies in the position normally filled by the guanidinium group of Arg244, present in most non-ESBL enzymes but absent from K1. The ammonium group of Lys276, ca 3.5 A from the virtual Arg244 guanidinium position, may interact with polar R2 substitutents on the dihydrothiazene ring of cephalosporins.

   View More

---

Organizational Affiliation: 

Department of Molecular and Cell Biology, The University of Connecticut, Storrs, CT 06269-3125, USA.