5hv1: Difference between revisions
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==Rifampin phosphotransferase in complex with AMPPNP and rifampin from Listeria monocytogenes== | ==Rifampin phosphotransferase in complex with AMPPNP and rifampin from Listeria monocytogenes== | ||
<StructureSection load='5hv1' size='340' side='right' caption='[[5hv1]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='5hv1' size='340' side='right'caption='[[5hv1]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5hv1]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5hv1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Listeria_monocytogenes Listeria monocytogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HV1 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.103Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RFP:RIFAMPICIN'>RFP</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=5hv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hv1 OCA], [https://pdbe.org/5hv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hv1 RCSB], [https://www.ebi.ac.uk/pdbsum/5hv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hv1 ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5hv1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5hv1" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Listeria monocytogenes]] | ||
[[Category: | [[Category: Qi X]] | ||
[[Category: | [[Category: Zhang P]] | ||
Revision as of 13:54, 16 August 2023
Rifampin phosphotransferase in complex with AMPPNP and rifampin from Listeria monocytogenesRifampin phosphotransferase in complex with AMPPNP and rifampin from Listeria monocytogenes
Structural highlights
Publication Abstract from PubMedRifampin (RIF) is a first-line drug used for the treatment of tuberculosis and other bacterial infections. Various RIF resistance mechanisms have been reported, and recently an RIF-inactivation enzyme, RIF phosphotransferase (RPH), was reported to phosphorylate RIF at its C21 hydroxyl at the cost of ATP. However, the underlying molecular mechanism remained unknown. Here, we solve the structures of RPH fromListeria monocytogenes(LmRPH) in different conformations. LmRPH comprises three domains: an ATP-binding domain (AD), an RIF-binding domain (RD), and a catalytic His-containing domain (HD). Structural analyses reveal that the C-terminal HD can swing between the AD and RD, like a toggle switch, to transfer phosphate. In addition to its catalytic role, the HD can bind to the AD and induce conformational changes that stabilize ATP binding, and the binding of the HD to the RD is required for the formation of the RIF-binding pocket. A line of hydrophobic residues forms the RIF-binding pocket and interacts with the 1-amino, 2-naphthol, 4-sulfonic acid and naphthol moieties of RIF. The R group of RIF points toward the outside of the pocket, explaining the low substrate selectivity of RPH. Four residues near the C21 hydroxyl of RIF, His825, Arg666, Lys670, and Gln337, were found to play essential roles in the phosphorylation of RIF; among these the His825 residue may function as the phosphate acceptor and donor. Our study reveals the molecular mechanism of RIF phosphorylation catalyzed by RPH and will guide the development of a new generation of rifamycins. Structural basis of rifampin inactivation by rifampin phosphotransferase.,Qi X, Lin W, Ma M, Wang C, He Y, He N, Gao J, Zhou H, Xiao Y, Wang Y, Zhang P Proc Natl Acad Sci U S A. 2016 Mar 21. pii: 201523614. PMID:27001859[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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