Quantum mechani cal investigation of the catalytic mechanism and inhibition of the dinuclear zinc metallo -ȕ-lactamase by penicillin

It is known that bacterial resis tance to ȕ-lactam antibi otics stems from the expression of the ȕ-lactam ase that c atalyzes the hydrolytic cleavage of the substra amid b ond. Metallo- ȕ-lactam ase contains zinc and other divalent cations as cofactors. The active site includes two zinc i ons, both of which are re quired for full catalytic activity, briging hydrox ide ion, Figure ۱. Since the initial d iscovery of inhibitors, a number of new inhibitors of met allo-ȕ-lactamase, antibi otics, have b een discovered [۱, ۲]. B esides the large amount of experimental work, a few theoretical studies on the din uclear zinc metallo-ȕ-lactamase hav e reported. Therefore, in the presen t study the coordination structure of active sit e dizinc center, catalytic mechanis m and inhibitor (penicillin) binding b ased on qua ntum calculations have investigated

کلیدواژه ها:

Metallo ȕ-lactamase ، Penicili ne ، Catalytic Mechanis m ، QM calc ulations