Intramolecular orbital alignments in serine protease/protein inhibitor complexes.
By an analysis of PDB crystal structures, the mean conformations of protein strands bound in serine protease active sites are shown to contain extensively aligned atomic orbitals. The active-serine-bearing segment of each enzyme (subtilisin BPN' and beta-trypsin) also contains such alignments. The participating orbitals are almost identical in each system. All of the alignments converge on the targeted linkage. They suggest that a kind of through-strand polarizability is being optimized by evolution, presumably due to corresponding benefits in proteolysis rate. Such polarizability would help to explain the high values of kcat seen for long oligopeptide substrates. The idea predicts long substrates to be relatively reactive even under non-enzymatic conditions, which in fact they are.
Fan
Yun-Hua
YH
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
Grégoire
Claire-Anne
CA
Haseltine
John
J
D001665:Binding Sites; D030562:Databases, Protein; D011485:Protein Binding; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D020860:Subtilisin / Q000737:chemistry / Q000502:physiology; D014357:Trypsin / Q000737:chemistry / Q000502:physiology
D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D014357:Trypsin; D020860:Subtilisin