1.9 Å x‐ray study shows closed flap conformation in crystals of tethered HIV‐1 PR

Three‐dimensional structure of an asymmetrically mutated (C95M) tethered human immunodeficiency virus type 1 protease enzyme (HIV‐1 PR) has been determined in an unliganded form using X‐ray diffraction data to 1.9 Å resolution. The structure, refined using X‐PLOR to an R factor of 19.5%, is unexpectedly similar to the ligand‐bound native enzyme, rather than to the ligand‐free native enzyme. In particular, the two flaps in the tethered dimer are in a closed configuration. The environments around M95 and C1095 are identical, showing no structural effect of this asymmetric mutation at position 95. Oxidation of Cys1095 has been observed for the first time. There is one well‐defined water molecule that hydrogen bonds to both carboxyl groups of the essential aspartic acids in the active site. Proteins 2001;43:57–64. © 2001 Wiley‐Liss, Inc.

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