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Science 1 December 1989:
Vol. 246. no. 4934, pp. 1149 - 1152
DOI: 10.1126/science.2686029
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Articles

Science, Vol 246, Issue 4934, 1149-1152
Copyright © 1989 by American Association for the Advancement of Science

articles

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

M Miller, J Schneider, BK Sathyanarayana, MV Toth, GR Marshall, L Clawson, L Selk, SB Kent, and A Wlodawer

NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, MD 21701.

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.


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