HIGH-RESOLUTION STRUCTURES OF HIV-1 RT FROM 4 RT-INHIBITOR COMPLEXES

We have determined the structures of four complexes of HIV-1 reverse t ranscriptase with non-nucleoside inhibitors, three fully refined at hi gh resolution. The highest resolution structure is of the RT-nevirapin e complex which has an R-factor of 0.186 and a root-mean-square bond l ength deviation of 0.015 Angstrom for all data to 2.2 Angstrom. The st ructures reveal a common mode of binding for these chemically diverse compounds. The common features of binding are largely hydrophobic inte ractions and arise from induced shape complementarity achieved by conf ormational rearrangement of the enzyme and conformational/ configurati onal rearrangement of the compounds.