Quantum chemical modeling of the GTP hydrolysis by the RAS-GAP protein complex.
Biochim Biophys Acta
; 1700(1): 125-36, 2004 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-15210132
ABSTRACT
We present results of the modeling for the hydrolysis reaction of guanosine triphosphate (GTP) in the RAS-GAP protein complex using essentially ab initio quantum chemistry methods. One of the approaches considers a supermolecular cluster composed of 150 atoms at a consistent quantum level. Another is a hybrid QM/MM method based on the effective fragment potential technique, which describes interactions between quantum and molecular mechanical subsystems at the ab initio level of the theory. Our results show that the GTP hydrolysis in the RAS-GAP protein complex can be modeled by a substrate-assisted catalytic mechanism. We can locate a configuration on the top of the barrier corresponding to the transition state of the hydrolysis reaction such that the straightforward descents from this point lead either to reactants GTP+H(2)O or to products guanosine diphosphate (GDP)+H(2)PO(4)(-). However, in all calculations such a single-step process is characterized by an activation barrier that is too high. Another possibility is a two-step reaction consistent with formation of an intermediate. Here the Pgamma-O(Pbeta) bond is already broken, but the lytic water molecule is still in the pre-reactive state. We present arguments favoring the assumption that the first step of the GTP hydrolysis reaction in the RAS-GAP protein complex may be assigned to the breaking of the Pgamma-O(Pbeta) bond prior to the creation of the inorganic phosphate.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Activadoras de ras GTPasa
/
Guanosina Trifosfato
/
Modelos Químicos
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos