Unusual role of Tyr588 of neuronal nitric oxide synthase in controlling substrate specificity and electron transfer

Yuko Sato, Ikuko Sagami, Toshitaka Matsui, Toru Shimizu

研究成果: Article査読

12 被引用数 (Scopus)

抄録

Nitric oxide (NO) is synthesized from L-Arg via NG-hydroxyl-L-Arg (NHA) in the heine active site of nitric oxide synthase (NOS). According to the crystal structure of other NOS isoforms, the carboxylate group of L-Arg hydrogen bonds to the hydroxyl group of the conserved Tyr588 residue in the heme distal site of neuronal NOS (nNOS). Indeed, the nNOS mutations Tyr588His, Tyr588Ser, and Tyr588Phe markedly increased the dissociation constants for L-Arg and NHA by 2.2-8.2-fold and 1.5-3.9-fold, respectively. Similarly, Tyr588His and Tyr588Ser mutations markedly decreased the L-Arg-driven NO formation rates by 50 and 30% than that of the wild type, respectively. However, the catalytic activities of the same mutants using NHA were higher than that of the wild type by up to 136%. As a result, the turnover ratio of NHA to L-Arg was 4.12 for the Tyr588Ser mutant, compared with 1.07 for the wild-type enzyme. Intriguingly, heme reduction rates for the Tyr588 mutants were much lower than for wild type by two orders of magnitude.

本文言語English
ページ(範囲)621-626
ページ数6
ジャーナルBiochemical and biophysical research communications
281
3
DOI
出版ステータスPublished - 2001

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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