Title : Crystal structure of human
renal dipeptidase involved in beta-lactam hydrolysis
Abstract :
- Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing dipeptides and is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics
- The crystal structures of the saccharide-trimmed enzyme are determined as unliganded and inhibitor-liganded forms
- They are informative for designing new antibiotics that are not hydrolyzed by this enzyme
- The active site in each of the (alpha/beta)(8) barrel subunits of the homodimeric molecule is composed of binuclear zinc ions bridged by the Glu125 side- chain located at the bottom of the barrel, and it faces toward the microvillar membrane of a kidney tubule
- A dipeptidyl moiety of the therapeutically used cilastatin inhibitor is fully accommodated in the active-site pocket, which is small enough for precise recognition of dipeptide substrates
- The barrel and active-site architectures utilizing catalytic metal ions exhibit unexpected similarities to those of the murine adenosine deaminase and the catalytic domain of the bacterial urease