Linked Life Data

2695163

Source:http://linkedlifedata.com/resource/pubmed/id/2695163

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
1990-3-27
pubmed:abstractText
Cow and rat trypsin differ in net charge by 12.5 units yet have the same enzymatic mechanism. The role of electrical potentials in the catalytic mechanism of these trypsin isozymes is investigated by using the finite difference Poisson-Boltzmann method. The calculations reveal that the active sites are effectively shielded from surface charge, thus making it possible for the two enzymes to have essentially identical potentials in their catalytically important regions. The potentials in both active sites are dominated by local interactions arising both from partial charges and from the negative charge on Asp-102. The latter is found to stabilize the transition state by about 4 kcal/mol, a value that is consistent with the extent of reduced catalytic activity in the variant Asn-102 trypsin, in which the negative charge is absent. The calculations predict that Asp-102 is ionized and that His-57 is neutral in the resting state of the enzyme. In contrast to their negligible effect on catalytic activity, the cumulative effect of surface charges is found to raise the pK of the N-terminal alpha-amino group of Ile-16 in the rat enzyme by about 1.5 units relative to that of cow trypsin. This charged amino acid forms an ionic bond with Asp-194, which stabilizes the active conformation of the enzyme. An increase in pK of Ile-16 thus provides a possible explanation for the retention of activity of rat trypsin at high pH. The results of this study could not have been obtained from an electrostatic model based on Coulombic potentials.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9918-26
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Electrical potentials in trypsin isozymes.
pubmed:affiliation
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10027.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.