Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Å resolution

Maria Miller, Jens Schneider, Bangalore K. Sathyanarayana, Mihaly V. Toth, Garland R. Marshall, Leigh Clawson, Linda Selk, Stephen B.H. Kent, Alexander Wlodawer

Research output: Contribution to journalArticlepeer-review

646 Scopus citations

Abstract

The structure of a complex between a peptide inhibitor with the sequence N-acetyl-Thr-Ile-Nle-Ψ[CH2-NH]-Nle-Gln-Arg.amide (Nle, norleucine) with chemically synthesized HIV-1 (human immunodeficiency virus 1) protease was determined at 2.3 Å resolution (R actor 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 Å are observed.

Original languageEnglish
Pages (from-to)1149-1152
Number of pages4
JournalScience
Volume246
Issue number4934
DOIs
StatePublished - 1989

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