Kinetic mechanism of the Rtt109-Vps75 histone acetyltransferase-chaperone complex.

ABSTRACT: Rtt109 is a histone acetyltransferase (HAT) involved in promoting genomic stability, DNA repair, and transcriptional regulation. Rtt109 associates with the NAP1 family histone chaperone Vps75 and stimulates histone acetylation. Here we explore the mechanism of histone acetylation and report a detailed kinetic investigation of the Rtt109-Vps75 complex. Rtt109 and Vps75 form a stable complex with nanomolar binding affinity (K(d) = 10 +/- 2 nM). Steady-state kinetic analysis reveals evidence of a sequential kinetic mechanism whereby the Rtt109-Vps75 complex, AcCoA, and histone H3 substrates form a complex prior to chemical catalysis. Product inhibition studies demonstrate that CoA binds competitively with AcCoA, and equilibrium measurements reveal AcCoA or CoA binding is not stimulated in the

SUBMITTER: Albaugh BN 

PROVIDER: S-EPMC2917178 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature