Date of Award
Fall 12-5-2025
Track
Chemistry
Degree Type
Thesis
Degree Name
Master of Science in Chemical Sciences (MSCB)
Department
Chemistry
Committee Chair/First Advisor
John Haseltine
Committee Member
Carol Chrestensen
Committee Member
Daniela Tapu
Abstract
An analysis of geometry in known serine protease crystal structures was conducted to give insight into the structural similarities of the ‘oxyanion holes’ in trypsin and subtilisin. The mean conformations of segments forming the oxyanion holes of these enzymes indicated that almost all of their relevant torsions are within 20° of creating ideal, extensive orbital alignments throughout their sequences. We propose that these alignments are available for dynamic through-bond electronics and may accommodate transient oxyanionic character during the formation and hydrolysis of the acyl-enzyme intermediate in proteolysis. We also carried out ab initio modeling using the Spartan software to analyze charge accommodation in various oligomeric molecular backbones as a function of strand length, heteroatom and pi-bond content, and conformation. In doing so, we were able to explore the possible importance of these factors in charge accommodation. In the crystal structures, we also considered the possibility of dynamic orbital splicing between the enzymes and their substrates. This allows us to develop a new rationale for the geometric similarities in serine proteases and speculate on active-site dynamics during the proteolytic mechanism.
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