QSAR analysis of the subtilisin hydrolysis of X-phenyl hippurates. II. A study of subtilisin BPN'.
The hydrolysis of 30 substituted phenyl hippurates (X-C6H4OCOCH2NHCOC6H5) by subtilisin BPN' was studied and from the results the following quantitative structure-activity relationship was derived: log 1/Km = 0.39 sigma + 0.16 B5.4 + 0.29 pi'3 + 3.58. In this expression Km is the Michaelis constant, sigma is the Hammett constant, B5.4 is the sterimol steric parameter of X in the 4-position and pi'3 is the hydrophobic parameter for the more hydrophobic of the two possible meta substituents. The other meta substitutent is assigned a pi value of 0. This mathematical model is qualitatively compared with a molecular graphics model constructed from the X-ray crystallographic coordinates of subtilisin BPN'. The results with subtilisin BPN' are compared with our earlier study of similar substrates with Carlsberg subtilisin.
Carotti
A
A
Department of Pharmaceutical Chemistry, University of Bari, Italy.
Raguseo
C
C
Klein
T E
TE
Langridge
R
R
Hansch
C
C
D003196:Computer Graphics; D006626:Hippurates / Q000378:metabolism; D007700:Kinetics; D013329:Structure-Activity Relationship; D013381:Subtilisins / Q000378:metabolism*
D006626:Hippurates; D013381:Subtilisins; C030514:hippuric acid