Characterizing the membrane-bound state of cytochrome P450 3A4: structure, depth of insertion, and orientation.

ABSTRACT: Cytochrome P450 3A4 (CYP3A4) is the most abundant membrane-associated isoform of the P450 family in humans and is responsible for biotransformation of more than 50% of drugs metabolized in the body. Despite the large number of crystallographic structures available for CYP3A4, no structural information for its membrane-bound state at an atomic level is available. In order to characterize binding, depth of insertion, membrane orientation, and lipid interactions of CYP3A4, we have employed a combined experimental and simulation approach in this study. Taking advantage of a novel membrane representation, highly mobile membrane mimetic (HMMM), with enhanced lipid mobility and dynamics, we have been able to capture spontaneous binding and insertion of the globular domain of the enzyme into the m

SUBMITTER: Baylon JL 

PROVIDER: S-EPMC3682445 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature