Author/Authors :
Vincent Stoll، نويسنده , , Wenying Qin، نويسنده , , Kent D. Stewart، نويسنده , , Clarissa Jakob، نويسنده , , Chang Park، نويسنده , , K. Walter، نويسنده , , R.L. Simmer، نويسنده , , Rosalind Helfrich، نويسنده , , Dirk Bussiere، نويسنده , , J. Kao، نويسنده , , Dale Kempf، نويسنده , , Hing L. Sham، نويسنده , , Daniel W. Norbeck، نويسنده ,
Abstract :
The crystal structure of ABT-378 (lopinavir), bound to the active site of HIV-1 protease is described. A comparison with crystal structures of ritonavir, A-78791, and BILA-2450 shows some analogous features with previous reported compounds. A cyclic urea unit in the P2 position of ABT-378 is novel and makes two bidentate hydrogen bonds with Asp 29 of HIV-1 protease. In addition, a previously unreported shift in the Gly 48 carbonyl position is observed. A discussion of the structural features responsible for its high potency against wild-type HIV protease is given along with an analysis of the effect of active site mutations on potency in in vitro assays.
