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Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
88
53-POS
Board 13
Generation and Assessment of Dynamic Structural Ensembles of Parvulin-type Peptidyl-
Prolyl Isomerases by Externally Restrained Molecular Dynamics Simulation
Bertalan Kovács
1
, András Czajlik
1
, Perttu Permi
2
, Zoltán Gáspári
1
.
1
Pázmány Péter Catholic University, Budapest, Hungary,
2
University of Jyväskylä, Jyväskylä,
Finland.
Parvulins are a subtype of peptidyl-prolyl isomerases (PPIase) that catalyze the isomerization of
the peptide bond preceding proline residues. They play a critical role in several biological
processes like chromatin remodeling, transcription and nuclear receptor signaling, as well as in
protein folding. While their three dimensional structure and the location of the active site is well-
defined, the exact mechanism of their catalytic activity remains elusive. It is generally accepted
that there is no breaking and reforming of the peptide bond, instead, isomerisation occurs
through a twisted intermediate state. A recent analysis of dynamic structural ensembles of
cyclophilin A proposed an electrostatic handle mechanism facilitated by the polarity of the
carbonyl group of the peptide bond.
In the presented study, externally restrained dynamical structural ensembles were generated
using experimentally determined NOEs and S2 parameters for three distinct parvulins: SaPrsA,
TbPin1 and CsPinA. The resulting ensembles show good agreement with the experimental
parameters, including chemical shifts, but also show significant differences in the dynamics of
the three enzymes.
Analysis of the predominant motional modes in both the restrained and unrestrained ensembles
as well as the role of the WW-domain in Pin1-type parvulins compared to the non-Pin1-type
suggest a catalitically determining motion in the enzyme activity. It is concluded that modulation
of the extent and dynamics of the identified motion accounts for the differences in the function of
the distinct parvulins. The presented results were recently published in Czajlik et al. 2017, Sci
Rep.