Abstract
Structures of 79 proteins involved in human diseases were predicted by sequence alignments with structural templates. The predicted structures for ALDP and CSA, proteins responsible for adrenoleukodystrophy and the Cockayne syndrome, respectively, were analyzed to elucidate the molecular basis of disease mutations. In particular we positioned residue P484 of ALDP in the homodimer interface. This positioning is consistent with a recent experimental finding that the mutation P484R significantly decreases the self-interaction of ALDP and suggests that the disease mechanism of this mutation lies in the impaired ALDP dimerization. We identified two new WD repeats in CSA and suggest that one of these forms part of the interaction surface with other proteins.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily D, Member 1
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ATP-Binding Cassette Transporters / chemistry*
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ATP-Binding Cassette Transporters / genetics
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Adenosine Triphosphate / metabolism
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Adrenoleukodystrophy / genetics
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Cockayne Syndrome / genetics
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DNA Repair Enzymes
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Dimerization
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Humans
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Membrane Proteins / chemistry*
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Membrane Proteins / genetics
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Models, Molecular
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Mutation
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Proteins / chemistry*
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Proteins / genetics
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Software
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Transcription Factors
Substances
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ABCD1 protein, human
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ATP Binding Cassette Transporter, Subfamily D, Member 1
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ATP-Binding Cassette Transporters
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ERCC8 protein, human
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Membrane Proteins
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Proteins
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Transcription Factors
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Adenosine Triphosphate
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DNA Repair Enzymes