Jose Cosme

TL;DR: The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound, and an unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.

TL;DR: The crystal structure of a human CYP450, CYP2C9, both unliganded and in complex with the anti-coagulant drug warfarin is described and a new binding pocket is discovered that suggests that CYP 2C9 may simultaneously accommodate multiple ligands during its biological function, and provides a possible molecular basis for understanding complex drug–drug interactions.

TL;DR: The first structure of a mammalian microsomal P450 was described in this article, which suggests that the association of P450s with the endoplasmic reticulum involves a hydrophobic surface of the protein formed by noncontiguous portions of the polypeptide chain.

TL;DR: The structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 is described and some of the drug discovery strategies employed in the identification of AT13387, which has progressed through preclinical development and is currently being tested in man.

TL;DR: These conditionally membrane-bound P450s with improved solubility in high salt buffers are suitable for crystallization and structural determination by x-ray diffraction studies.