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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. September 2004, Volume 3, Number 9, 560-571 |
The Influence of Sequence Variability and Dimerization on Mannose
Binding in Monocot Mannose Binding Lectins
Anna C. Tanczos, David A. Faux, David C. Povey, and Brendan J. Howlin
Internet Electron. J. Mol. Des. 2004, 3, 560-571
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Abstract:
A model of the lectin from Aloe arborescens was built by
homology modeling. Docking studies with mannose were
performed on this model and the known crystal structures of
monocot mannose binding lectins from snowdrop and garlic. On
the basis of these results association of monomers to form dimers
is found to be necessary for successful binding of mannose by site
III of these lectins, by providing the fourth strand of the β-sheet
that is a supporting edge for the site. From an analysis of the
carbohydrate binding sites (I, II and III) of the above lectins and
the docking studies, the mannose binding site I of aloe lectin is
predicted to retain the ability to bind mannose with all of the key
residues involved in binding unchanged. Site II and III lose
residues specific for hydrogen bonding and are predicted to be
unable to bind mannose. Aloe lectin monomers are shown to be
able to associate as dimers but docking is still unsuccessful in site
III. Protein homology modeling and AutoDock docking studies
were used in this study. A homology model of aloe lectin was
created by both manual and automatic methods and its ability to
bind the natural substrate mannose was assessed by docking
studies using the genetic algorithm approach in the AutoDock
program. The results of the docking studies were correlated with
those on lectins for which X-ray crystal data is known and
rationalized in terms of specific mutations in the aloe lectin
binding sites. Aloe lectin is predicted to be able to bind mannose in
its site I binding site, unable to bind in site II because of key
residue mutations and also unable to bind in site III.
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