Convergent Chemical Synthesis and Crystal Structure of a 203 Amino Acid “Covalent Dimer” HIV-1 Protease Enzyme Molecule

Authors

  • Vladimir Yu. Torbeev,

    1. Department of Chemistry, Institute for Biophysical Dynamics, Gordon Center for Integrative Science, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA, Fax: (+1) 773-702-0439
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  • Stephen B. H. Kent Prof. Dr.

    1. Department of Chemistry, Institute for Biophysical Dynamics, Gordon Center for Integrative Science, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA, Fax: (+1) 773-702-0439
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  • We acknowledge funding from the DOE “Genomics to Life” program (grant no. DE-FG02-04ER63786). Use of the Advanced Photon Source (Argonne, IL) was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract no. W-31-109-Eng-38. Use of the GM/CA-CAT beamline has been funded in whole or in part with Federal funds from the National Cancer Instutute (Y1-CO-1020) and the National Institute of General Medical Sciences (Y1-GM-1104). We acknowledge the help and advice from Dr. Valentina A. Terechko (University of Chicago) on X-ray structure refinement.

Abstract

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Synthesizing enzymes: The great potential of recently developed methods for the fully convergent chemical synthesis of proteins has been demonstrated by the synthesis of the 203 amino acid “covalent dimer” HIV-1 protease (see picture). The 21 870 Da protein synthesized has full enzymatic activity and the correct three-dimensional structure, as demonstrated by high-resolution X-ray crystallographic analysis.

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