Picosecond to second dynamics reveals a structural transition in clostridium botulinum no-sensor triggered by the activator BAY-41-2272

Byung-Kuk Yoo 1 Isabelle Lamarre 1 Fabrice Rappaport 2 Pierre Nioche 3 C.S. Raman 4 Jean-Louis Martin 1 Michel Negrerie 1, *
* Corresponding author
1 LOB - Laboratoire d'optique et biosciences
2 Institut de Biologie Physico-Chimie
3 Laboratoire de Toxicologie et Pharmacologie
4 Department of Pharmaceutical Sciences
Abstract : Soluble guanylate cyclase (sGC) is the mammalian endogenous nitric oxide (NO) receptor that synthesizes cGMP upon NO activation. In synergy with the artificial allosteric effector BAY 41-2272 (a lead compound for drug design in cardiovascular treatment), sGC can also be activated by carbon monoxide (CO), but the structural basis for this synergistic effect are unknown. We recorded in the unusually broad time range from 1 ps to 1 s the dynamics of the interaction of CO binding to full length sGC, to the isolated sGC heme domain ß1(200) and to the homologous bacterial NO-sensor from Clostridium botulinum. By identifying all phases of CO binding in this full time range and characterizing how these phases are modified by BAY 41-2272, we show that this activator induces the same structural changes in both proteins. This result demonstrates that the BAY 41-2272 binding site resides in the ß1(200) sGC heme domain and is the same in sGC and in the NO-sensor from Clostridium botulinum. Cop. 2012 American Chemical Society.
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Submitted on : Thursday, April 25, 2013 - 10:18:26 PM
Last modification on : Thursday, February 7, 2019 - 5:00:36 PM

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Byung-Kuk Yoo, Isabelle Lamarre, Fabrice Rappaport, Pierre Nioche, C.S. Raman, et al.. Picosecond to second dynamics reveals a structural transition in clostridium botulinum no-sensor triggered by the activator BAY-41-2272. ACS Chemical Biology, American Chemical Society, 2012, 7 (12), pp.2046-2054. ⟨10.1021/cb3003539⟩. ⟨hal-00817164⟩

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