Complexes of glucoamylase with maltoside heteroanalogues: bound ligand conformations by use of transferred NOE experiments and molecular modeling

Thomas Weimar, Bjarne Stoffer, Birte Svensson, B. Mario Pinto

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Transferred nuclear Overhauser effect (trNOE) experiments have been performed to investigate the conformations of the competitive inhibitors, methyl 5'-thio-4-N-alpha-maltoside 3a and methyl 5'-thio-4-S-alpha-maltoside 4 when bound to the catalytic subunit of the enzyme glucoamylase. These NMR data suggest that, although each of the free ligands populates two conformational families, both heteroanalogues are bound by the enzyme in conformations in the area of the global energy minimum. These conformations have been used as initial points for docking into the active site of the enzyme taken from a X-ray crystal structure of the related glucoamylase-D-gluco-dihydroacarbose 2 complex. Minimization of the resulting complexes has yielded structures for the bound complexes. Corroboration of the structures is provided by fast T(1)(rho)-relaxation effects for certain ligand protons as a result of close contacts with protons in the enzyme active site. The results auger well for the combined use of transferred NOE spectroscopy and molecular modeling based on X-ray crystal structures of complexes of suitable congeners for the rapid analysis of ligand-receptor interactions.
Original languageEnglish
JournalBiochemistry
Volume39
Issue number2
Pages (from-to)300-306
ISSN0006-2960
DOIs
Publication statusPublished - 2000
Externally publishedYes

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