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PDBsum entry 1mz3
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Structural protein
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PDB id
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1mz3
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References listed in PDB file
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Key reference
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Title
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Prediction of possible sites for posttranslational modifications in human gamma crystallins: effect of glycation on the structure of human gamma-B-Crystallin as analyzed by molecular modeling.
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Authors
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A.Salim,
A.Bano,
Z.H.Zaidi.
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Ref.
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Proteins, 2003,
53,
162-173.
[DOI no: ]
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PubMed id
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Abstract
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Crystallins are recognized as one of the long-lived proteins of lens tissue that
might serve as the target for several posttranslational modifications leading to
cataract development. We have studied several such sites present in the human
gamma-crystallins based either on PROSITE pattern search results or earlier
experimental evidences. Their probabilities were examined on the basis of the
database analysis of the gamma-crystallin sequences and on their specific
locations in the constructed homology models. An N-glycosylation site in human
gammaD-crystallin and several phosphorylation sites in all four human
gamma-crystallins were predicted by the PROSITE search. Some of these sites were
found to be strongly conserved in the gamma-crystallin sequences from different
sources. An extensive analysis of these sites was performed to predict their
probabilities as potential sites for protein modifications. Glycation studies
were performed separately by attaching sugars to the human gammaB-crystallin
model, and the effect of binding was analyzed. The studies showed that the major
effect of alphaD-glucose (alphaD-G) and alphaD-glucose-6-phosphate (alphaD-G6P)
binding was the disruption of charges not only at the surface but also within
the molecule. Only a minor alteration in the distances of sulfhydryl groups of
cysteines and on their positions in the three-dimensional models were observed,
leading us to assume that glycation alone is not responsible for intra- and
intermolecular disulfide bond formation.
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Figure 1.
Figure 1. CLUSTAL W multiple-sequence alignment of  -crystallin
sequences from human, bovine, rat, and mouse retrieved from the
SWISS PROT data bank. Predicted patterns containing specific
sites for posttranslational modifications in -crystallin
are highlighted. Not all of these sites identified by the
PROSITE search were conserved throughout the sequence. Sites
that are strongly conserved in the database of -crystallin
sequences are marked by arrows.
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Figure 3.
Figure 3. Possible phosphorylation sites (shown in ball and
stick) as predicted by their positions in the homology models
(a) human A-crystallin:
Ser87, Tyr98, Tyr154, and Thr171; (b) human C-crystallin:
Tyr65 and Ser87; and (c) human D-crystallin:
Ser87 and Tyr98.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2003,
53,
162-173)
copyright 2003.
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