View source for 9mxy


==Pseudomonas fluorescens isocyanide hydratase D17N mutant, pH=6.5==
<StructureSection load='9mxy' size='340' side='right'caption='[[9mxy]], [[Resolution|resolution]] 1.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9mxy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9MXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MXY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9mxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mxy OCA], [https://pdbe.org/9mxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mxy RCSB], [https://www.ebi.ac.uk/pdbsum/9mxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mxy ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A complete understanding of enzyme mechanisms requires atomistic details of chemical reactions. Quantum-based molecular dynamics simulations (QMD) are a potential source of this information, but trade-offs between accuracy and computational cost have limited their use. We previously developed extended Lagrangian Born-Oppenheimer molecular dynamics (XL-BOMD) methods that leverage a negligible compromise in accuracy to substantially decrease the cost of QMD simulations. Here, we develop a reactive QMD approach using the latest XL-BOMD formulation, which enables efficient simulations of highly reactive systems, and use it to investigate mechanisms of intermediate formation in isocyanide hydratase (ICH) catalysis. In QMD simulations, molecular analogs of ICH active site residues reacted with para-nitrophenyl isocyanide, forming a thioimidate. Analysis of simulated atomic configurational and charge dynamics revealed a pathway where protonation of the isocyanide carbon occurs prior to thioimidate formation and suggested a possible role of Asp17 as a proton donor in the early phase of ICH catalysis. To test whether the pathway seen using the reactive QMD approach might be relevant to ICH catalysis, we performed X-ray crystallography and pre-steady-state enzyme kinetics studies of wild-type and D17N mutant ICH. Both the structure and kinetics are sensitive to the D17N mutation in a manner that is consistent with the order of the reaction steps seen in the simulations. Mobile protons play essential roles in many enzymes, yet they are difficult to observe experimentally, making the ordering of proton-dependent steps ambiguous in many enzyme mechanisms. The ability to directly simulate model reactions for the design of experiments that provide information about enzyme mechanisms involving mobile protons demonstrates the significance of our reactive QMD approach and motivates further biological applications.

Combining Reactive Quantum-Mechanical Molecular-Dynamics Simulations with Mutagenesis, Crystallography, and Enzyme Kinetics to Reveal Plausible Steps of Isocyanide Hydratase Catalysis.,Corrigan Grove RA, Moxley MA, Negre CFA, Cawkwell MJ, Niklasson AMN, Mniszewski SM, Smith N, Prososki K, Wilson MA, Wall ME J Chem Inf Model. 2025 Oct 27;65(20):11079-11093. doi: 10.1021/acs.jcim.5c01152. , Epub 2025 Oct 6. PMID:41051317<ref>PMID:41051317</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9mxy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas fluorescens]]
[[Category: Prososki K]]
[[Category: Smith N]]
[[Category: Wilson MA]]