title: Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution.
abstract: The structure of a complex between a peptide inhibitor with the sequence N-acetyl-Thr-Ile-Nle-psi[CH2-NH]-Nle-Gln-Arg.amide (Nle, norleucine) with chemically synthesized HIV-1 (human immunodeficiency virus 1) protease was determined at 2.3 A resolution (R factor of 0.176). Despite the symmetric nature of the unliganded enzyme, the asymmetric inhibitor lies in a single orientation and makes extensive interactions at the interface between the two subunits of the homodimeric protein. Compared with the unliganded enzyme, the protein molecule underwent substantial changes, particularly in an extended region corresponding to the "flaps" (residues 35 to 57 in each chain), where backbone movements as large as 7 A are observed.
authors.affiliation: NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, MD 21701.
authors.forename: M
authors.initials: M
authors.lastname: Miller
authors.forename: J
authors.initials: J
authors.lastname: Schneider
authors.forename: B K
authors.initials: BK
authors.lastname: Sathyanarayana
authors.forename: M V
authors.initials: MV
authors.lastname: Toth
authors.forename: G R
authors.initials: GR
authors.lastname: Marshall
authors.forename: L
authors.initials: L
authors.lastname: Clawson
authors.forename: L
authors.initials: L
authors.lastname: Selk
authors.forename: S B
authors.initials: SB
authors.lastname: Kent
authors.forename: A
authors.initials: A
authors.lastname: Wlodawer
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D010450:Endopeptidases / Q000378:metabolism*; D015683:Gene Products, gag / Q000378:metabolism; D016333:HIV Protease; D015497:HIV-1 / Q000201:enzymology*; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D015683:Gene Products, gag; D009842:Oligopeptides; D011480:Protease Inhibitors; C061946:MVT 101; D010450:Endopeptidases; D016333:HIV Protease