The DOI matches its Crossref record.
Structure of Complex of Synthetic HIV-1 Protease with a Substrate-Based Inhibitor at 2.3 Å Resolution
Abstract
The structure of a complex between a peptide inhibitor with the sequence N -acetyl-Thr-Ile-Nle-ψ[ CH 2 -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 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 Å are observed.
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Cited by
INHIBITORS OF HIV-1 PROTEASE: A Major Success of Structure-Assisted Drug Design
Wlodawer, A., & Vondrasek, J. (1998) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.27.1.249 · Cited by 734
Self-citationJaskolski, M., Tomasselli, A. G., Sawyer, T. K., Staples, D. G., Heinrikson, R. L., Schneider, J., Kent, S. B. H., & Wlodawer, A. (1991) · Biochemistry · doi:10.1021/bi00220a023 · Cited by 227
Self-citationStructural and biochemical studies of retroviral proteases
Wlodawer, A., & Gustchina, A. (2000) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(99)00267-8 · Cited by 166
Self-citationUnderstanding the Molecular Basis of Apert Syndrome
Ibrahimi, O. A., Chiu, E. S., McCarthy, J. G., & Mohammadi, M. (2005) · Plastic & Reconstructive Surgery · doi:10.1097/01.prs.0000146703.08958.95 · Cited by 88
Greives, N., & Zhou, H.-X. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407545111 · Cited by 82
Metadata
- Authors
- Miller, M., Schneider, J., Sathyanarayana, B. K., Toth, M. V., Marshall, G. R., Clawson, L., Selk, L., Kent, S. B. H., & Wlodawer, A.
- Venue
- Science
- Published
- 1989-12
- Volume
- 246
- Issue
- 4934
- Pages
- 1149-1152
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2087876594
- Cited by
- 684
- References
- 0
- FWCI
- 62.06
- Type
- journal article
- Language
- en
- Open access
- closed
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