scholarly journals Exploring water as building bricks in enzyme engineering

2015 ◽  
Vol 51 (97) ◽  
pp. 17221-17224 ◽  
Author(s):  
Peter Hendil-Forssell ◽  
Mats Martinelle ◽  
Per-Olof Syrén
Keyword(s):  
Transition State ◽  
Enzyme Catalysis ◽  
De Novo ◽  
Enzyme Engineering ◽  
Transition State Stabilization

A de novo designed water pattern is used to achieve a 34-fold accelerated promiscuous enzyme catalysis by efficient transition state stabilization.

Insights into enzyme catalysis from QM/MM modelling: transition state stabilization in chorismate mutase

2003 ◽  
Vol 101 (17) ◽  
pp. 2695-2714 ◽  
Author(s):  
KARA E. RANAGHAN ◽  
LARS RIDDER ◽  
BORYS SZEFCZYK ◽  
W. ANDRZEJ SOKALSKI ◽  
JOHANNES C. HERMANN ◽  
...  
Keyword(s):  
Transition State ◽  
Enzyme Catalysis ◽  
Chorismate Mutase ◽  
Transition State Stabilization

Transition state stabilization and substrate strain in enzyme catalysis: ab initio QM/MM modelling of the chorismate mutase reaction

2004 ◽  
Vol 2 (7) ◽  
pp. 968 ◽  
Author(s):  
Kara E. Ranaghan ◽  
Lars Ridder ◽  
Borys Szefczyk ◽  
W. Andrzej Sokalski ◽  
Johannes C. Hermann ◽  
...  
Keyword(s):  
Transition State ◽  
Ab Initio ◽  
Enzyme Catalysis ◽  
Chorismate Mutase ◽  
Transition State Stabilization ◽  
Substrate Strain

scholarly journals An alternative view of enzyme catalysis

2005 ◽  
Vol 77 (11) ◽  
pp. 1873-1886 ◽  
Author(s):  
Fredric M. Menger
Keyword(s):  
Transition State ◽  
Enzyme Catalysis ◽  
Alternative View ◽  
Spatiotemporal Model ◽  
Substrate Complex ◽  
Site Model ◽  
Enzyme Substrate ◽  
Transition State Stabilization ◽  
Computational Data ◽  
The Many

This paper begins with a brief review of theories and concepts that have influenced today's view of enzyme catalysis: transition-state stabilization, entropy, orbital steering, proximity, and intramolecularity. The discussion then launches into the "spatiotemporal" model of enzyme catalysis in which fast intramolecular and enzymatic rates are ascribed to short distances that are imposed rigidly upon the reacting entities. An equation relating rate and distance is set forth, as are experimental and computational data supporting this relationship. Finally, enzyme systems themselves are analyzed in terms of the distance parameter and the so-called "split-site" model in which ground-state geometries play a crucial role. Among the many surprising conclusions is a transition-state stabilization by noncovalent forces (e.g., hydrogen-bonding) that are positioned far away from the actual transition-state chemistry. The model also confronts and dismisses the claim in classical enzymology that the ubiquitous enzyme-substrate complex is either inconsequential or inhibitory to the overall reaction rate.

scholarly journals Crystal structures of non-oxidative decarboxylases reveal a new mechanism of action with a catalytic dyad and structural twists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthias Zeug ◽  
Nebojsa Markovic ◽  
Cristina V. Iancu ◽  
Joanna Tripp ◽  
Mislav Oreb ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Active Site ◽  
Enzyme Engineering ◽  
Base Catalysis ◽  
Oxidative Decarboxylation ◽  
Transition State Stabilization ◽  
Major Bottleneck ◽  
Hydroxybenzoic Acids ◽  
Potassium Binding ◽  
Β Sheet

AbstractHydroxybenzoic acids, like gallic acid and protocatechuic acid, are highly abundant natural compounds. In biotechnology, they serve as critical precursors for various molecules in heterologous production pathways, but a major bottleneck is these acids’ non-oxidative decarboxylation to hydroxybenzenes. Optimizing this step by pathway and enzyme engineering is tedious, partly because of the complicating cofactor dependencies of the commonly used prFMN-dependent decarboxylases. Here, we report the crystal structures (1.5–1.9 Å) of two homologous fungal decarboxylases, AGDC1 from Arxula adenivorans, and PPP2 from Madurella mycetomatis. Remarkably, both decarboxylases are cofactor independent and are superior to prFMN-dependent decarboxylases when heterologously expressed in Saccharomyces cerevisiae. The organization of their active site, together with mutational studies, suggests a novel decarboxylation mechanism that combines acid–base catalysis and transition state stabilization. Both enzymes are trimers, with a central potassium binding site. In each monomer, potassium introduces a local twist in a β-sheet close to the active site, which primes the critical H86-D40 dyad for catalysis. A conserved pair of tryptophans, W35 and W61, acts like a clamp that destabilizes the substrate by twisting its carboxyl group relative to the phenol moiety. These findings reveal AGDC1 and PPP2 as founding members of a so far overlooked group of cofactor independent decarboxylases and suggest strategies to engineer their unique chemistry for a wide variety of biotechnological applications.

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