Solution conformation of a cyclophilin-bound proline isomerase substrate.
Cyclophilin (CyP) is the 17.8-kDa cytosolic receptor of the immunosuppressant cyclosporin A (CsA) and also a peptidyl prolyl cis-trans isomerase (PPIase). In order to gain insights into the PPIase mechanism, transferred nuclear Overhauser effect (TRNOE) measurements by two-dimensional 1H NMR were used to determine the conformation of the isomerase-bound standard model substrate suc-AAPF-pNA. Results indicate a cis-like conformation for the CyP-bound substrate with the A-P peptide bond being no more than 40 degrees out of planarity.
Kakalis
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Department of Pharmacology, Yale University Medical School, New Haven, Connecticut 06520-8066.
Armitage
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D000591:Amino Acid Isomerases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003903:Deuterium; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D019696:Peptidylprolyl Isomerase; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D012996:Solutions
D002352:Carrier Proteins; D009842:Oligopeptides; D011994:Recombinant Proteins; D012996:Solutions; C043307:succinyl-alanyl-alanyl-prolyl-phenylalanine-4-nitroanilide; D003903:Deuterium; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase