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10.1074/jbc.AC120.016154 http://scihub22266oqcxt.onion/10.1074/jbc.AC120.016154 33060199!7832724!33060199     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2020 ; 295 (50): 17365-17373 Nephropedia Template TP {{tp|p=33060199|t=2020. Unusual zwitterionic catalytic site of SARS-CoV-2 main protease revealed by neutron crystallography |pdf=|usr=}}{{33060199}} gab.com Text Unusual zwitterionic catalytic site of SARS-CoV-2 main protease revealed by neutron crystallography JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=33060199 #FOAvip The main protease (3CL M(pro)) from SARS-CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication. 3CL M(pro) possesses an unusual catalytic dyad composed of Cys(145) and His(41) residues. A critical question in the field has been what the protonation states of the ionizable residues in the substrate-binding active-site cavity are; resolving this point would help understand the catalytic details of the enzyme and inform rational drug development against this pernicious virus. Here, we present the room-temperature neutron structure of 3CL M(pro), which allowed direct determination of hydrogen atom positions and, hence, protonation states in the protease. We observe that the catalytic site natively adopts a zwitterionic reactive form in which Cys(145) is in the negatively charged thiolate state and His(41) is doubly protonated and positively charged, instead of the neutral unreactive state usually envisaged. The neutron structure also identified the protonation states, and thus electrical charges, of all other amino acid residues and revealed intricate hydrogen-bonding networks in the active-site cavity and at the dimer interface. The fine atomic details present in this structure were made possible by the unique scattering properties of the neutron, which is an ideal probe for locating hydrogen positions and experimentally determining protonation states at near-physiological temperature. Our observations provide critical information for structure-assisted and computational drug design, allowing precise tailoring of inhibitors to the enzyme's electrostatic environment. Twit Text FOAVip Unusual zwitterionic catalytic site of SARS-CoV-2 main protease revealed by neutron crystallography ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=33060199 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33060199 #FOAvip English Wikipedia <ref>{{Cite pmid|33060199}}</ref> Unusual zwitterionic catalytic site of SARS-CoV-2 main protease revealed by neutron crystallography #MMPMID33060199 Kneller DW; Phillips G; Weiss KL; Pant S; Zhang Q; O'Neill HM; Coates L; Kovalevsky A J Biol Chem 2020[Dec]; 295 (50): 17365-17373 PMID33060199show ga The main protease (3CL M(pro)) from SARS-CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication. 3CL M(pro) possesses an unusual catalytic dyad composed of Cys(145) and His(41) residues. A critical question in the field has been what the protonation states of the ionizable residues in the substrate-binding active-site cavity are; resolving this point would help understand the catalytic details of the enzyme and inform rational drug development against this pernicious virus. Here, we present the room-temperature neutron structure of 3CL M(pro), which allowed direct determination of hydrogen atom positions and, hence, protonation states in the protease. We observe that the catalytic site natively adopts a zwitterionic reactive form in which Cys(145) is in the negatively charged thiolate state and His(41) is doubly protonated and positively charged, instead of the neutral unreactive state usually envisaged. The neutron structure also identified the protonation states, and thus electrical charges, of all other amino acid residues and revealed intricate hydrogen-bonding networks in the active-site cavity and at the dimer interface. The fine atomic details present in this structure were made possible by the unique scattering properties of the neutron, which is an ideal probe for locating hydrogen positions and experimentally determining protonation states at near-physiological temperature. Our observations provide critical information for structure-assisted and computational drug design, allowing precise tailoring of inhibitors to the enzyme's electrostatic environment. |*Models, Molecular[MESH] |*Neutrons[MESH] |Catalytic Domain[MESH] |Coronavirus 3C Proteases/*chemistry[MESH] |Crystallography, X-Ray[MESH]Unusual zwitterionic catalytic site of SARS-CoV-2 main protease reveal(epmc).pdf DeepDyve Pubget Overpricing