Protein backbone engineering through total chemical synthesis: New insight into the mechanism of HIV-1 protease catalysis
- Details
- Publication Year 2000-11-24,Volume 56,Issue #48,Page 9503-9513
- Journal Title
- TETRAHEDRON
- Publication Type
- Journal Article
- Abstract
- Total chemical synthesis by convergent chemical ligation was used to prepare a 'backbone engineered' 202-residue covalent dimer asymmetric form of the HIV-1 protease molecule. The Gly49-Ile50 peptide bond backbone -N(H)- atom, critically involved in H-bonding to substrates, was specifically replaced by an -O- atom in one flap only. The resulting enzyme analogue retained full intrinsic activity, demonstrating that enzyme-substrate hydrogen bonding at the Gly49-Ile50 peptide bond in only a single flap is sufficient for normal catalytic function. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- IMMUNODEFICIENCY-VIRUS INFECTION; SOLID-PHASE SYNTHESIS; CRYSTAL-STRUCTURE; ASPARTIC PROTEINASES; CRYSTALLOGRAPHIC STRUCTURE; RETROVIRAL PROTEASES; ENHANCED STABILITY; KINETIC-PROPERTIES; VIRAL INFECTIVITY; TYPE-1 PROTEASE
- Publisher's Version
- https://doi.org/10.1016/S0040-4020(00)00835-8
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-11-24 12:00:00