Abstract：
:alpha-D-glucose is a weak inhibitor (Ki = 1.7 mM) of glycogen phosphorylase (GP) and acts as physiological regulator of hepatic glycogen metabolism; it binds to GP at the catalytic site and stabilizes the inactive T state of the enzyme promoting the action of protein phosphatase 1 and stimulating glycogen synthase. The three-dimensional structures of T state rabbit muscle GPb and the GPb-alpha-D-glucose complex have been exploited in the design of better regulators of GP that could shift the balance between glycogen synthesis and glycogen degradation in favour of the former. Close examination of the catalytic site with alpha-D-glucose bound shows that there is an empty pocket adjacent to the beta-1-C position. beta-D-glucose is a poorer inhibitor (Ki = 7.4 mM) than alpha-D-glucose, but mutarotation has prevented the binding of beta-D-glucose in T state GP crystals. A series of beta-D-glucose analogues has been designed and tested in kinetic and crystallographic experiments. Several compounds have been discovered that have an increased affinity for GP than the parent compound.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Oikonomakos NG,Kontou M,Zographos SE,Tsitoura HS,Johnson LN,Watson KA,Mitchell EP,Fleet GW,Son JC,Bichard CJdoi
10.1007/BF03188920subject
Has Abstract,Author List Incompletepub_date
1994-07-01 00:00:00pages
185-92issue
3eissn
0378-7966issn
2107-0180journal_volume
19pub_type
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