2015
DOI: 10.1016/j.bbagen.2014.12.023
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Computational perspective and evaluation of plausible catalytic mechanisms of peptidyl-prolyl cis–trans isomerases

Abstract: Fully understanding the catalytic mechanism of PPIases has broad implications for drug design, elucidation of the molecular basis of many diseases, protein engineering, and enzyme catalysis in general. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets.

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Cited by 14 publications
(17 citation statements)
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References 102 publications
(168 reference statements)
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“…The catalytic mechanism of PPIases does not involve any bond formation or breakage, but hinges instead on rotation around the peptidyl-prolyl bond, which is at least partially mediated by preferential stabilization of the twisted transition state [ 9 , 10 ]. In the case of the cyclophilins, there has been some debate as to whether it is the part N- or C-terminal to the peptidyl-prolyl bond that rotates [ 36 38 ].…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The catalytic mechanism of PPIases does not involve any bond formation or breakage, but hinges instead on rotation around the peptidyl-prolyl bond, which is at least partially mediated by preferential stabilization of the twisted transition state [ 9 , 10 ]. In the case of the cyclophilins, there has been some debate as to whether it is the part N- or C-terminal to the peptidyl-prolyl bond that rotates [ 36 38 ].…”
Section: Discussionmentioning
confidence: 99%
“…Nature has therefore evolved three families of peptidyl-prolyl isomerases (PPIases) to facilitate cis / trans isomerization: FK506-binding proteins (FKBPs), cyclophilins, and parvulins [ 8 , 9 ]. These enzymes presumably all function by stabilizing the transition state, resulting in an effective rate constant for the catalyzed reaction of up to 10 8 M −1 s −1 [ 9 ], but their mechanisms are not well understood [ 9 , 10 ].…”
Section: Introductionmentioning
confidence: 99%
“…In contrast, peptidyl-prolyl cis-trans isomerase (PPIase) and its subunits were up-regulated in V79 cells cultured in the DUGL. PPIase represents a rate limiting step in protein folding, catalyses cis to trans isomerization of peptidyl prolyl bonds [37,38] and is involved in many biological processes. PPIase has been implicated in stress tolerance in wheat; therefore, PPIase activity in V79 cells may have been responsible for enhanced protection against decreased background radiation [37].…”
Section: Discussionmentioning
confidence: 99%
“…45 Cis-trans isomerization is slow and is catalyzed by PPIases through stabilization of the transition state without the formation or the breakage of any covalent bond. 46 Interaction of CypA with Cyclosporine A, an immunosuppressive and antirejection drug that is often given to patients after organ transplants, 47 lowers the T-cell activation and thus the immune response. There is an increasing number of reports that specifically link CypA to various types of cancers 48 mainly due to their over-expression, suggesting a potential prognostic role for CypA.…”
Section: Enhanced Sampling Of Potential Drug Targets With Acceleratedmentioning
confidence: 99%
“…Cyclophilin A (CypA) belongs to the ubiquitous family of peptidyl prolyl cis – trans isomerases (PPIases) that is known to be involved in a host of biochemical processes such as protein folding, regulation of apoptosis, molecular chaperone activity, protection of mitochondria, and eliciting the immune response by binding to the transmembrane protein CD147 . Cis – trans isomerization is slow and is catalyzed by PPIases through stabilization of the transition state without the formation or the breakage of any covalent bond . Interaction of CypA with Cyclosporine A, an immunosuppressive and anti‐rejection drug that is often given to patients after organ transplants, lowers the T‐cell activation and thus the immune response.…”
Section: Introductionmentioning
confidence: 99%