Clarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV-1 protease.

ABSTRACT: The 1TW7 crystal structure of HIV-1 protease shows the flaps placed wider and more open than what is seen in other examples of the semi-open, apo form. It has been proposed that this might be experimental evidence of allosteric control, because crystal packing creates contacts to the "elbow region" of the protease, which may cause deformation of the flaps. Recent dynamics simulations have shown that the conformation seen in 1TW7 relaxes into the typical semi-open conformation in the absence of the crystal contacts, definitively showing that the crystal contacts cause the deformation (Layten et al., J Am Chem Soc 2006;128:13360-13361). However, this does not prove or disprove allosteric modulation at the elbow. In this study, we have conducted additional simulations, supplemented with exper

SUBMITTER: Lexa KW 

PROVIDER: S-EPMC2635929 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature