The mechanism of the elongation and branching reaction of poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis.
J Mol Biol
; 278(1): 57-65, 1998 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-9571033
ABSTRACT
The binding site for the acceptor substrate poly(ADP-ribose) in the elongation reaction of the ADP-ribosyl transferase poly(ADP-ribose) polymerase (PARP) was detected by cocrystallizing the enzyme with an NAD+ analogue. The site was confirmed by mutagenesis studies. In conjunction with the binding site of the donor NAD+, the bound acceptor reveals the geometry of the elongation reaction. It shows in particular that the strictly conserved glutamate residue of all ADP-ribosylating enzymes (Glu988 of PARP) facilitates the reaction by polarizing both, donor and acceptor. Moreover, the binding properties of the acceptor site suggest a mechanism for the branching reaction, that also explains the dual specificity of this transferase for elongation and branching, which is unique among polymer-forming enzymes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poli(ADP-Ribose) Polimerases
/
NAD
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Alemanha