Browsing by Author "Khalid, Rana Rehan"

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    Cryo-EM density map fitting driven in-silico structure of human soluble guanylate cyclase (hsGC) reveals functional aspects of inter-domain cross talk upon NO binding
    (ELSEVIER SCIENCE INC, 2019-01-01) Khalid, Rana Rehan; Maryam, Arooma; Fadouloglou, Vasiliki E.; Siddiqi, Abdul Rauf; Zhang, Yang
    The human soluble Guanylate Cyclase (hsGC) is a heterodimeric heme-containing enzyme which regulates many important physiological processes. In eukaryotes, hsGC is the only known receptor for nitric oxide (NO) signaling. Improper NO signaling results in various disease conditions such as neuro-degeneration, hypertension, stroke and erectile dysfunction. To understand the mechanisms of these diseases, structure determination of the hsGC dimer complex is crucial. However, so far all the attempts for the experimental structure determination of the protein were unsuccessful. The current study explores the possibility to model the quaternary structure of hsGC using a hybrid approach that combines state-of-the-art protein structure prediction tools with cryo-EM experimental data. The resultant 3D model shows close consistency with structural and functional insights extracted from biochemistry experiment data. Overall, the atomic-level complex structure determination of hsGC helps to unveil the inter-domain communication upon NO binding, which should be of important usefulness for elucidating the biological function of this important enzyme and for developing new treatments against the hsGC associated human diseases. (C) 2019 Elsevier Inc. All rights reserved.
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    Probing the Structural Dynamics of the Catalytic Domain of Human Soluble Guanylate Cyclase
    (NATURE PUBLISHING GROUP, 2020-01-01) Khalid, Rana Rehan; Maryam, Arooma; Sezerman, Osman Ugur; Mylonas, Efstratios; Siddiqi, Abdul Rauf; Kokkinidis, Michael
    In the nitric oxide (NO) signaling pathway, human soluble guanylate cyclase (hsGC) synthesizes cyclic guanosine monophosphate (cGMP)