Extending crystallographic information with semiempirical quantum mechanics and molecular mechanics: a case of aspartic proteinases.
The results of crystallographic analysis of a complex between an aspartic proteinase, endothiapepsin, and an inhibitor have been extended through the assignment of protons in the active site, to study various steps in the reaction with a substrate. Mechanistic implications are suggested as a consequence of semiempirical quantum mechanical calculations, indicating that most of the activation energy is required to bring the substrate from an initial binding mode to close distance to a water molecule.
Department of Pharmaceutical Chemistry, School of Pharmacy, Hebrew University of Jerusalem, Israel.
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Goldblum
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Rayan
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Fliess
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Glick
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001665:Binding Sites; D016333:HIV Protease / Q000737:chemistry; D015497:HIV-1 / Q000201:enzymology; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011522:Protons; D011789:Quantum Theory; D013816:Thermodynamics; D014961:X-Ray Diffraction
D011522:Protons; D016282:Aspartic Acid Endopeptidases; C042466:Endothia aspartic proteinase; D016333:HIV Protease