"Structural Basis of Biological Nitrile Reduction."
Chikwana VM, Stec B, Lee BW, de Crecy-Lagard V, Iwata-Reuyl D, Swairjo MA
Published 2012-07-11 in J Biol Chem .
Pubmed ID: 22787148
DOI identifier: -
|The enzyme QueF catalyzes the reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ0) to 7-aminomethyl-7-deazaguanine (preQ1), the only nitrile reduction reaction known in Biology. We describe here two crystal structures of Bacillus subtilis QueF, one of the wild-type enzyme in complex with the substrate preQ0, trapped as a covalent thioimide, a putative intermediate in the reaction, and the second of the Cys55Ala mutant in complex with the substrate preQ0 bound non-covalently. The QueF enzyme forms an asymmetric tunnel-fold homodecamer of two head-to-head facing pentameric subunits, harboring ten active sites at the inter-subunit interfaces. In both structures a preQ0 molecule is bound at eight sites, and in the wild-type enzyme it forms a thioimide covalent linkage to the catalytic residue Cys55. Both structural and transient kinetic data show that preQ0 binding, not thioimide formation, induces a large conformational change in and closure of the active site. Based on these data we propose a mechanism for the activation of the Cys55 nucleophile and subsequent hydride transfer.|
This publication refers to following proteins:
- QueF (Bacillus subtilis)
Last modification of this entry: Sept. 6, 2012