Fine-tuning the extent and dynamics of binding cleft opening as a potential general regulatory mechanism in parvulin-type peptidyl prolyl isomerases
Czajlik, A., Kovács, B., Permi, P., & Gáspári, Z. (2017). Fine-tuning the extent and dynamics of binding cleft opening as a potential general regulatory mechanism in parvulin-type peptidyl prolyl isomerases. Scientific Reports, 7, 44504. doi:10.1038/srep44504
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Scientific ReportsDate
2017Copyright
© the Authors, 2017. This is an open access article distributed under under a Creative Commons Attribution 4.0 International License.
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 S2 order 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.
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