Important roles of Tyr43 at the putative heme distal side in the oxygen recognition and stability of the Fe(II)-O2 complex of YddV, a globin-coupled heme-based oxygen sensor diguanylate cyclase

Kenichi Kitanishi, Kazuo Kobayashi, Yuriko Kawamura, Izumi Ishigami, Takashi Ogura, Kyosuke Nakajima, Jotaro Igarashi, Atsunari Tanaka, Toru Shimizu

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Abstract

YddV from Escherichia coli (Ec) is a novel globin-coupled heme-based oxygen sensor protein displaying diguanylate cyclase activity in response to oxygen availability. In this study, we quantified the turnover numbers of the active [Fe(III), 0.066 min-1; Fe(II)-O2 and Fe(II)-CO, 0.022 min-1] [Fe(III), Fe(III)-protoporphyrin IX complex; Fe(II), Fe(II)-protoporphyrin IX complex] and inactive forms [Fe(II) and Fe(II)-NO, <0.01 min-1] of YddV for the first time. Our data indicate that the YddV reaction is the rate-determining step for two consecutive reactions coupled with phosphodiesterase Ec DOS activity on cyclic di-GMP (c-di-GMP) [turnover number of Ec DOS-Fe(II)-O2, 61 min-1]. Thus, O2 binding and the heme redox switch of YddV appear to be critical factors in the regulation of c-di-GMP homeostasis. The redox potential and autoxidation rate of heme of the isolated heme domain of YddV (YddV-heme) were determined to be -17 mV versus the standard hydrogen electrode and 0.0076 min-1, respectively. The Fe(II) complexes of Y43A and Y43L mutant proteins (residues at the heme distal side of the isolated heme-bound globin domain of YddV) exhibited very low O2 affinities, and thus, their Fe(II)-O2 complexes were not detected on the spectra. The O 2 dissociation rate constant of the Y43W protein was >150 s -1, which is significantly larger than that of the wild-type protein (22 s-1). The autoxidation rate constants of the Y43F and Y43W mutant proteins were 0.069 and 0.12 min-1, respectively, which are also markedly higher than that of the wild-type protein. The resonance Raman frequencies representing vFe-O2 (559 cm-1) of the Fe(II)-O2 complex and vFe-CO (505 cm-1) of the Fe(II)-CO complex of Y43F differed from those (vFe-O2, 565 cm -1; vFe-CO, 495 cm-1) of the wild-type protein, suggesting that Tyr43 forms hydrogen bonds with both O2 and CO molecules. On the basis of the results, we suggest that Tyr43 located at the heme distal side is important for the O2 recognition and stability of the Fe(II)-O2 complex, because the hydroxyl group of the residue appears to interact electrostatically with the O2 molecule bound to the Fe(II) complex in YddV. Our findings clearly support a role of Tyr in oxygen sensing, and thus modulation of overall conversion from GTP to pGpG via c-di-GMP catalyzed by YddV and Ec DOS, which may be applicable to other globin-coupled oxygen sensor enzymes.

Original languageEnglish (US)
Pages (from-to)10381-10393
Number of pages13
JournalBiochemistry
Volume49
Issue number49
DOIs
StatePublished - Dec 14 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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