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Published on: February 16, 2022
Structural basis of biological nitrile reduction
Vimbai M Chikwana1, Boguslaw Stec, Bobby W K Lee
1Department of Chemistry, Portland State University, Portland, OR 97207, USA.
The Journal of Biological Chemistry
|July 13, 2012
Summary
The enzyme QueF reduces a nitrile group in a unique biological reaction. Structural studies reveal how substrate binding, not covalent linkage, triggers key enzyme conformational changes for catalysis.
Area of Science:
- Biochemistry
- Enzymology
- Structural Biology
Background:
- The enzyme QueF catalyzes the sole known biological nitrile reduction.
- This reaction converts 7-cyano-7-deazaguanine (preQ(0)) to 7-aminomethyl-7-deazaguanine (preQ(1)).
Purpose of the Study:
- To elucidate the structural mechanisms of QueF-catalyzed nitrile reduction.
- To understand the role of substrate binding and covalent intermediate formation in enzyme activation.
Main Methods:
- X-ray crystallography of Bacillus subtilis QueF wild-type and C55A mutant enzymes.
- Complex formation with the substrate preQ(0).
- Transient kinetic analysis.
Main Results:
- Two crystal structures were obtained: wild-type QueF with a covalent thioimide intermediate and C55A mutant with noncovalently bound preQ(0).
- QueF forms an asymmetric homodecamer with active sites at subunit interfaces.
- Substrate binding, rather than thioimide formation, induces significant active site conformational changes and closure.
Conclusions:
- A mechanism for QueF-catalyzed nitrile reduction is proposed.
- The findings highlight the importance of substrate-induced conformational changes in enzyme catalysis.
- This work provides insights into a unique biological nitrile reduction pathway.
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