Unknown

Dataset Information

0

Structural basis of biological nitrile reduction.


ABSTRACT: The enzyme QueF catalyzes the reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ(0)) to 7-aminomethyl-7-deazaguanine (preQ(1)), 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 preQ(0), trapped as a covalent thioimide, a putative intermediate in the reaction, and the second of the C55A mutant in complex with the substrate preQ(0) bound noncovalently. The QueF enzyme forms an asymmetric tunnel-fold homodecamer of two head-to-head facing pentameric subunits, harboring 10 active sites at the intersubunit interfaces. In both structures, a preQ(0) molecule is bound at eight sites, and in the wild-type enzyme, it forms a thioimide covalent linkage to the catalytic residue Cys-55. Both structural and transient kinetic data show that preQ(0) 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 Cys-55 nucleophile and subsequent hydride transfer.

SUBMITTER: Chikwana VM 

PROVIDER: S-EPMC3436371 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural basis of biological nitrile reduction.

Chikwana Vimbai M VM   Stec Boguslaw B   Lee Bobby W K BW   de Crécy-Lagard Valérie V   Iwata-Reuyl Dirk D   Swairjo Manal A MA  

The Journal of biological chemistry 20120711 36


The enzyme QueF catalyzes the reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ(0)) to 7-aminomethyl-7-deazaguanine (preQ(1)), 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 preQ(0), trapped as a covalent thioimide, a putative intermediate in the reaction, and the second of the C55A mutant in complex with the substrate preQ(0) bound noncovalently. The Q  ...[more]

Similar Datasets

| S-EPMC3922912 | biostudies-literature
| S-EPMC3894310 | biostudies-literature
| S-EPMC10237034 | biostudies-literature
| S-EPMC4306959 | biostudies-literature
| S-EPMC3999263 | biostudies-literature
| S-EPMC7696479 | biostudies-literature
2015-06-10 | E-GEOD-67730 | biostudies-arrayexpress
| S-EPMC4298667 | biostudies-literature
| S-EPMC7472224 | biostudies-literature
| S-EPMC4960239 | biostudies-literature