title: Structural basis for HTLV-1 protease inhibition by the HIV-1 protease inhibitor indinavir.
abstract: HTLV-1 protease (HTLV-1 PR) is an aspartic protease which represents a promising drug target for the discovery of novel anti-HTLV-1 drugs. The X-ray structure of HTLV-1 PR in complex with the well-known and approved HIV-1 PR inhibitor Indinavir was determined at 2.40 Å resolution. In this contribution, we describe the first crystal structure in complex with a nonpeptidic inhibitor that accounts for rationalizing the rather moderate affinity of Indinavir against HTLV-1 PR and provides the basis for further structure-guided optimization strategies.
authors.affiliation: Institut für Pharmazeutische Chemie, Philipps-Universität Marburg , Marbacher Weg 6, 35032 Marburg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Kuhnert
authors.forename: Holger
authors.initials: H
authors.lastname: Steuber
authors.forename: Wibke E
authors.initials: WE
authors.lastname: Diederich
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D019469:Indinavir / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D016282:Aspartic Acid Endopeptidases; C079711:HTLV-1 protease