scholarly journals Interplay of nucleophilic catalysis with proton transfer in the nitrile reductase QueF from Escherichia coli

2019 ◽  
Vol 9 (3) ◽  
pp. 842-853 ◽  
Author(s):  
Jihye Jung ◽  
Jan Braun ◽  
Tibor Czabany ◽  
Bernd Nidetzky
Keyword(s):  
Escherichia Coli ◽  
Hydrogen Bonds ◽  
Proton Transfer ◽  
Active Site ◽  
Nucleophilic Catalysis ◽  
Proton Relay ◽  
Network Of Hydrogen Bonds ◽  
Site Network ◽  
Nitrile Reduction ◽  
Enzyme Intermediate

Proton relay through an active-site network of hydrogen bonds promotes enzymatic nitrile reduction to amine via a covalent thioimidate enzyme intermediate.

WHICH IS THE PROTON-SHUTTLE IN ISOXANTHOPTERIN DEAMINASE? QM/MM MD UNDERSTANDING

2013 ◽  
Vol 12 (08) ◽  
pp. 1341002 ◽  
Author(s):  
XIN ZHANG ◽  
MING LEI
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Hydrogen Bonds ◽  
Proton Transfer ◽  
Glutamic Acid ◽  
Active Site ◽  
Nucleophilic Attack ◽  
Zinc Ions ◽  
Initial Model ◽  
Dynamics Simulations

The deamination process of isoxanthopterin catalyzed by isoxanthopterin deaminase was determined using the combined QM(PM3)/MM molecular dynamics simulations. In this paper, the updated PM3 parameters were employed for zinc ions and the initial model was built up based on the crystal structure. Proton transfer and following steps have been investigated in two paths: Asp336 and His285 serve as the proton shuttle, respectively. Our simulations showed that His285 is more effective than Aap336 in proton transfer for deamination of isoxanthopterin. As hydrogen bonds between the substrate and surrounding residues play a key role in nucleophilic attack, we suggested mutating Thr195 to glutamic acid, which could enhance the hydrogen bonds and help isoxanthopterin get close to the active site. The simulations which change the substrate to pterin 6-carboxylate also performed for comparison. Our results provide reference for understanding of the mechanism of deaminase and for enhancing the deamination rate of isoxanthopterin deaminase.

scholarly journals Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Christina M Zimanyi ◽  
Percival Yang-Ting Chen ◽  
Gyunghoon Kang ◽  
Michael A Funk ◽  
Catherine L Drennan
Keyword(s):  
Escherichia Coli ◽  
Hydrogen Bonds ◽  
Substrate Specificity ◽  
Ribonucleotide Reductase ◽  
Active Site ◽  
Molecular Basis ◽  
Allosteric Site ◽  
Dna Biosynthesis ◽  
Conformational Rearrangements ◽  
Proper Balance

Ribonucleotide reductase (RNR) converts ribonucleotides to deoxyribonucleotides, a reaction that is essential for DNA biosynthesis and repair. This enzyme is responsible for reducing all four ribonucleotide substrates, with specificity regulated by the binding of an effector to a distal allosteric site. In all characterized RNRs, the binding of effector dATP alters the active site to select for pyrimidines over purines, whereas effectors dGTP and TTP select for substrates ADP and GDP, respectively. Here, we have determined structures of Escherichia coli class Ia RNR with all four substrate/specificity effector-pairs bound (CDP/dATP, UDP/dATP, ADP/dGTP, GDP/TTP) that reveal the conformational rearrangements responsible for this remarkable allostery. These structures delineate how RNR ‘reads’ the base of each effector and communicates substrate preference to the active site by forming differential hydrogen bonds, thereby maintaining the proper balance of deoxynucleotides in the cell.

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