CONFORMATIONAL STUDY OF A PUTATIVE HTLV-1 RETROVIRAL PROTEASE INHIBITOR

The crystal structure of prolyl-glutaminyl-valyl-statyl-alanyl-leucine (Pro-Gln-Val-Sta-Ala-Leu, C32H57N7O9.-5H2O, M(r) = 683.9 + 90.1), a p utative HTLV-1 protease inhibitor based on one of the consensus retrov iral protease cleavage sequences, and containing the statine residue [ (4S,3S)-4-amino-3-hydroxy-6-methylheptanoic acid], has been determined by X-ray diffraction. The same molecule has been modelled in the acti ve site of the HTLV-1 protease and both conformations have been compar ed. The peptide crystallizes as a pentahydrate in space group P2(1) wi th a = 10.874(2), b = 9.501(2), c = 21.062(5) angstrom, beta = 103.68 (1)-degrees, Z = 2, V = 2114.3 angstrom3, D(x) = 1.21 g cm-3, mu = 8.0 2 cm-1, T = 293 K, lambda(Cu Kalpha) = 1.5418 angstrom. The structure has been refined to an R value of 0.070 for 2152 observed reflections. The peptide main chain can be described as extended and adopts the us ual zigzag conformation from the prolyl to the statyl residue. The mai n difference in conformation between the individual observed and model led molecules is located on the Sta, Ala and Leu residues with the mai n chain of the modelled molecule rotated by about 180-degrees as compa red to the observed conformation in the crystal state.