Prediction of substrate-specific pockets in cyclosporin synthetase.
Amino acid sequence comparisons between domains of cyclosporin synthetase have been used to identify regions of the sequence which are responsible for the recognition and binding of the individual amino acids. Using a limited set of selection rules it was possible to identify three amino acid positions in the subdomain sequences which are responsible for amino acid specificity. Homology with the firefly luciferase protein shows that these three key residues are close to each other and line the surface of a putative specific substrate binding pocket located on the amino acyl-adenylation subdomain. These results allow us to predict a large number of cyclosporin synthetase mutants which could be used to synthesise alternative cyclosporin-like peptides.
Husi
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Department of Biochemistry, The University of Edinburgh, UK.
Schörgendorfer
K
K
Stempfer
G
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Taylor
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P
Walkinshaw
M D
MD
D000595:Amino Acid Sequence; D001665:Binding Sites; D008156:Luciferases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D010453:Peptide Synthases / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D009097:Multienzyme Complexes; C048525:cyclosporin A synthetase; D008156:Luciferases; D010453:Peptide Synthases