title: Fine-tuning the extent and dynamics of binding cleft opening as a potential general regulatory mechanism in parvulin-type peptidyl prolyl isomerases.
abstract: Parvulins or rotamases form a distinct group within peptidyl prolyl cis-trans isomerases. Their exact mode of action as well as the role of conserved residues in the family are still not unambiguously resolved. Using backbone S2order parameters and NOEs as restraints, we have generated dynamic structural ensembles of three distinct parvulins, SaPrsA, TbPin1 and CsPinA. The resulting ensembles are in good agreement with the experimental data but reveal important differences between the three enzymes. The largest difference can be attributed to the extent of the opening of the substrate binding cleft, along which motional mode the three molecules occupy distinct regions. Comparison with a wide range of other available parvulin structures highlights structural divergence along the bottom of the binding cleft acting as a hinge during the opening-closing motion. In the prototype WW-domain containing parvulin, Pin1, this region is also important in forming contacts with the WW domain known to modulate enzymatic activity of the catalytic domain. We hypothesize that modulation of the extent and dynamics of the identified 'breathing motion' might be one of the factors responsible for functional differences in the distinct parvulin subfamilies.
authors.affiliation: Pázmány Péter Catholic University, Faculty of Information Technology and Bionics, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Czajlik
authors.affiliation: Pázmány Péter Catholic University, Faculty of Information Technology and Bionics, Budapest, Hungary.
authors.forename: Bertalan
authors.initials: B
authors.lastname: Kovács
authors.affiliation: University of Jyvaskyla, Dept. of Biological and Environmental Science, Dept. of Chemistry, Nanoscience Center, Jyvaskyla, Finland.
authors.forename: Perttu
authors.initials: P
authors.lastname: Permi
authors.affiliation: Pázmány Péter Catholic University, Faculty of Information Technology and Bionics, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Gáspári
mesh_terms: D000595:Amino Acid Sequence; D001105:Archaea / Q000201:enzymology; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000737:chemistry* / Q000235:genetics; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000201:enzymology; D014346:Trypanosoma brucei brucei / Q000201:enzymology
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase