IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Catalytic role of the metal ion in the metallo-beta-lactamase GOB
Autor/es:
MARÍA NATALIA LISA ; LARS HEMMINGSEN; ALEJANDRO J. VILA,
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Lugar: Bethesda; Año: 2010 vol. 285 p. 4570 - 4577
ISSN:
0021-9258
Resumen:
Metallo-beta-lactamases (M beta Ls) stand as one of the mainmechanisms of bacterial resistance toward carbapenems. Therational design of an inhibitor for M beta Ls has been limited byan incomplete knowledge of their catalytic mechanism and bythe structural diversity of their active sites. Here we show thatthe M beta L GOB from Elizabethkingia meningoseptica is activeas a monometallic enzyme by using different divalent transitionmetal ions as surrogates of the native Zn(II) ion. Of themetal derivatives in which Zn(II) is replaced, Co(II) andCd(II) give rise to the most active enzymes and are shown tooccupy the same binding site as the native ion. However,Zn(II) is the only metal ion capable of stabilizing an anionicintermediate that accumulates during nitrocefin hydrolysis,in which the C–N bond has already been cleaved. This findingdemonstrates that the catalytic role of the metal ion in GOB isto stabilize the formation of this intermediate prior to nitrogenprotonation. This role may be general to all M beta Ls,whereas nucleophile activation by a Zn(II) ion is not a conservedmechanistic feature.