Coordination of Alkyl Nitroso Compounds: Influence of Ligand Sterics on RNO Binding and Complex Stability in the Active Site of Myoglobin

Abstract

Event Abstract Back to Event Coordination of Alkyl Nitroso Compounds: Influence of Ligand Sterics on RNO Binding and Complex Stability in the Active Site of Myoglobin Viridiana E. Herrera1, Samantha M. Powell1, Jun Yi1, Bing Wang1, Leoonard M. Thomas1 and George B. Richter-Addo1* 1 University of Oklahoma, United States The main function of the muscle protein myoglobin (Mb) is oxygen storage. This is achieved by binding dioxygen (O2) reversibly at the iron center of the heme cofactor. Organic nitrosoalkanes (RNO; R = alkyl) are valence isoelectronic with O2, and not surprisingly, have demonstrated high affinities towards hemoproteins such as Mb, and often compete with O2 in the binding pocket to form “inhibitory” Fe(II)-RNO complexes. Several biologically relevant organic compounds contain the amine (RNH2) and/or nitro (RNO2) functional groups. Under normal or perturbed physiological conditions (e.g., during infection), nitrosoalkanes can results from the oxidative metabolism of amines/hydroxylamines (RNH2/RNHOH) or by the reduction of nitro-containing compounds. In human hemoglobin, the resultant binding of certain RNOs to the heme site may lead to methemoglobinemia or hemolytic anemia, and can cause detrimental heme loss and successive accumulation of Fe in the spleen. In human liver cytochrome P450, RNOs inhibit the same protein responsible for detoxification of xenobiotics. Although the issues described above pose serious health hazards, there is a paucity of information regarding the mode of binding of RNOs to hemoproteins such as Mb, and the architectural consequences of such binding to protein structure and function. With this in mind, we determined the effects of ligands sterics on RNO binding to Mb and the resulting stability of the complexes, by employing a series of RNOs with increasing bulk of the alkyl groups. Furthermore, to augment our findings, we elucidated the importance of distal pocket composition on ligand coordination and reactivity by incorporating the distal pocket mutant H64A into our research. We found that simple chemical changes to the active site, as well as the sterics of our ligands, significantly impact complex coordination and stability. Our resulting X-ray crystal structures and reactivity trends, as determined by UV-vis spectroscopy, will be presented and discussed. Acknowledgements Price Family Foundation Institute of Structural Biology, Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK Keywords: Structural Biology, Biochemistry, Myoglobin, nitroso alkanes, X-ray crystal and molecular structure Conference: National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference , Orlando, Florida, United States, 17 Sep - 20 Sep, 2018. Presentation Type: Oral Presentation Topic: Biochemistry Citation: Herrera VE, Powell SM, Yi J, Wang B, Thomas LM and Richter-Addo GB (2019). Coordination of Alkyl Nitroso Compounds: Influence of Ligand Sterics on RNO Binding and Complex Stability in the Active Site of Myoglobin. Front. Chem. Conference Abstract: National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference . doi: 10.3389/conf.fchem.2018.01.00042 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. George B Richter-Addo, University of Oklahoma, Norman, United States, grichteraddo@ou.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Viridiana E Herrera Samantha M Powell Jun Yi Bing Wang Leoonard M Thomas George B Richter-Addo Google Viridiana E Herrera Samantha M Powell Jun Yi Bing Wang Leoonard M Thomas George B Richter-Addo Google Scholar Viridiana E Herrera Samantha M Powell Jun Yi Bing Wang Leoonard M Thomas George B Richter-Addo PubMed Viridiana E Herrera Samantha M Powell Jun Yi Bing Wang Leoonard M Thomas George B Richter-Addo Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.