Monooxygenation of an appended phenol in a model system of tyrosinase: implications on the enzymatic reaction mechanism

2015 ◽  
Vol 44 (7) ◽  
pp. 3251-3258 ◽  
Author(s):  
Jessica Nadine Hamann ◽  
Malte Rolff ◽  
Felix Tuczek
Keyword(s):  
Reaction Mechanism ◽  
Enzymatic Reaction ◽  
Model System ◽  
New Model ◽  
Enzymatic Reaction Mechanism

A new model system of tyrosinase was established that performs an ortho-hydroxylation of the appended phenol in the absence of base.

Protein Structural Change upon Ligand Binding Correlates with Enzymatic Reaction Mechanism

2008 ◽  
Vol 379 (3) ◽  
pp. 397-401 ◽  
Author(s):  
Ryotaro Koike ◽  
Takayuki Amemiya ◽  
Motonori Ota ◽  
Akinori Kidera
Keyword(s):  
Structural Change ◽  
Reaction Mechanism ◽  
Ligand Binding ◽  
Enzymatic Reaction ◽  
Enzymatic Reaction Mechanism

Crystal structure analysis, refinement and enzymatic reaction mechanism of N-carbamoylsarcosine amidohydrolase from Arthrobacter sp. at 2·0Åresolution

1992 ◽  
Vol 226 (4) ◽  
pp. 1111-1130 ◽  
Author(s):  
Maria Joa˜o Roma˜o ◽  
Dusan Turk ◽  
Franz-Xaver Gomis-Rüth ◽  
Robert Huber ◽  
Günther Schumacher ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Reaction Mechanism ◽  
Structure Analysis ◽  
Enzymatic Reaction ◽  
Crystal Structure Analysis ◽  
Enzymatic Reaction Mechanism

scholarly journals Bovine Pancreatic Ribonuclease: Fifty Years of the First Enzymatic Reaction Mechanism

Biochemistry ◽  
2011 ◽  
Vol 50 (37) ◽  
pp. 7835-7841 ◽  
Author(s):  
Claudi M. Cuchillo ◽  
M. Victòria Nogués ◽  
Ronald T. Raines
Keyword(s):  
Reaction Mechanism ◽  
Enzymatic Reaction ◽  
Pancreatic Ribonuclease ◽  
Enzymatic Reaction Mechanism

scholarly journals Elucidation of Enzymatic Reaction Mechanism by Neutron Crystallography

2021 ◽  
Vol 61 (4) ◽  
pp. 216-222
Author(s):  
Fumiaki KONO ◽  
Kazuo KURIHARA ◽  
Taro TAMADA
Keyword(s):  
Reaction Mechanism ◽  
Enzymatic Reaction ◽  
Enzymatic Reaction Mechanism ◽  
Neutron Crystallography

scholarly journals Crystal Structure of 4-Hydroxyphenylpyruvate Dioxygenase in Complex with Substrate Reveals a New Starting Point for Herbicide Discovery

Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Hong-Yan Lin ◽  
Xi Chen ◽  
Jia-Nan Chen ◽  
Da-Wei Wang ◽  
Feng-Xu Wu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Reaction Mechanism ◽  
Enzymatic Reaction ◽  
Binding Mode ◽  
Active State ◽  
Site Directed Mutagenesis ◽  
Inactive State ◽  
Starting Point ◽  
New Strategy ◽  
Enzymatic Reaction Mechanism

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a promising target for drug and pesticide discovery. The unknown binding mode of substrate is still a big challenge for the understanding of enzymatic reaction mechanism and novel HPPD inhibitor design. Herein, we determined the first crystal structure of Arabidopsis thaliana HPPD (AtHPPD) in complex with its natural substrate (HPPA) at a resolution of 2.80 Å. Then, combination of hybrid quantum mechanics/molecular mechanics (QM/MM) calculations confirmed that HPPA takes keto rather than enol form inside the HPPD active pocket. Subsequent site-directed mutagenesis and kinetic analysis further showed that residues (Phe424, Asn423, Glu394, Gln307, Asn282, and Ser267) played important roles in substrate binding and catalytic cycle. Structural comparison between HPPA-AtHPPD and holo-AtHPPD revealed that Gln293 underwent a remarkable rotation upon the HPPA binding and formed H-bond network of Ser267-Asn282-Gln307-Gln293, resulting in the transformation of HPPD from an inactive state to active state. Finally, taking the conformation change of Gln293 as a target, we proposed a new strategy of blocking the transformation of HPPD from inactive state to active state to design a novel inhibitor with Ki value of 24.10 nM towards AtHPPD. The inhibitor has entered into industry development as the first selective herbicide used for the weed control in sorghum field. The crystal structure of AtHPPD in complex with the inhibitor (2.40 Å) confirmed the rationality of the design strategy. We believe that the present work provides a new starting point for the understanding of enzymatic reaction mechanism and the design of next generation HPPD inhibitors.

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