Inactivation of hypoxanthine guanine phosphoribosyltransferase by guanosine dialdehyde: An active site directed inhibitor

Johnson L.A., Gordon R.B. and Emmerson B.T. (1979) Inactivation of hypoxanthine guanine phosphoribosyltransferase by guanosine dialdehyde: An active site directed inhibitor. Biochemical medicine, 22 1: 33-42. doi:10.1016/0006-2944(79)90034-6


Author Johnson L.A.
Gordon R.B.
Emmerson B.T.
Title Inactivation of hypoxanthine guanine phosphoribosyltransferase by guanosine dialdehyde: An active site directed inhibitor
Journal name Biochemical medicine   Check publisher's open access policy
ISSN 0006-2944
Publication date 1979-01-01
Sub-type Article (original research)
DOI 10.1016/0006-2944(79)90034-6
Volume 22
Issue 1
Start page 33
End page 42
Total pages 10
Subject 1303 Specialist Studies in Education
Abstract Guanosine dialdehyde (GDA), the periodate oxidation product of guanosine, has been found to be a relatively specific, essentially irreversible, inhibitor of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). The inactivation reaction shows saturation kinetics, implicating the formation of a specific complex between enzyme and inhibitor. Saturating concentrations of magnesium phosphoribosylpyrophosphate, but not of hypoxanthine or guanine, protect the enzyme against inactivation by GDA. Inosine dialdehyde, the periodate oxidation product of inosine, also inhibits HGPRT but less effectively than GDA. Adenosine dialdehyde, the periodate oxidation product of adenosine, has no effect on HGPRT, although it does considerably inhibit adenine phosphoribosyltransferase. Adenine phosphoribosyltransferase and purine nucleoside phosphorylase are little affected by GDA. These results indicate that GDA is an activesite-directed inhibitor of HGPRT. This specific interaction between GDA and HGPRT is superimposed on nonspecific interactions between GDA and proteins which render the inhibitor unsuitable for use in vivo. However, the results suggest that suitable modification of the ribose moiety of guanosine may provide an in vivo-inactivating agent which might be used to produce animal models of HGPRT deficiency.
Q-Index Code C1
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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Created: Tue, 13 Sep 2016, 10:32:24 EST by System User