6unc
From Proteopedia
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(New page: '''Unreleased structure''' The entry 6unc is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The crystal structure of Phosphopantetheinyl Hydrolase (PptH) from Mycobacterium tuberculosis== |
| + | <StructureSection load='6unc' size='340' side='right'caption='[[6unc]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UNC 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]] 2.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=6unc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6unc OCA], [https://pdbe.org/6unc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6unc RCSB], [https://www.ebi.ac.uk/pdbsum/6unc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6unc ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The amidinourea 8918 was recently reported to inhibit the type II phosphopantetheinyl transferase (PPTase) of Mycobacterium tuberculosis (Mtb), PptT, a potential drug-target that activates synthases and synthetases involved in cell wall biosynthesis and secondary metabolism. Surprisingly, high-level resistance to 8918 occurred in Mtb harboring mutations within the gene adjacent to pptT, rv2795c, highlighting the role of the encoded protein as a potentiator of the bactericidal action of the amidinourea. Those studies revealed that Rv2795c (PptH) is a phosphopantetheinyl (PpT) hydrolase, possessing activity antagonistic with respect to PptT. We have solved the crystal structure of Mtb's phosphopantetheinyl hydrolase, making it the first phosphopantetheinyl (carrier protein) hydrolase structurally characterized. The 2.5 A structure revealed the hydrolases' four-layer (alpha/beta/beta/alpha) sandwich fold featuring a Mn-Fe binuclear center within the active site. A structural similarity search confirmed that PptH most closely resembles previously characterized metallophosphoesterases (MPEs), particularly within the vicinity of the active site, suggesting that it may utilize a similar catalytic mechanism. In addition, analysis of the structure has allowed for the rationalization of the previously reported PptH mutations associated with 8918-resistance. Notably, differences in the sequences and predicted structural characteristics of the PpT hydrolases PptH of Mtb and E. coli's acyl carrier protein hydrolase (AcpH) indicate that the two enzymes evolved convergently and therefore are representative of two distinct PpT hydrolase families. | ||
| - | + | Structural insights into phosphopantetheinyl hydrolase PptH from Mycobacterium tuberculosis.,Mosior J, Bourland R, Soma S, Nathan C, Sacchettini J Protein Sci. 2020 Mar;29(3):744-757. doi: 10.1002/pro.3813. Epub 2020 Jan 20. PMID:31886928<ref>PMID:31886928</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6unc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mosior JW]] | ||
| + | [[Category: Sacchettini JC]] | ||
Current revision
The crystal structure of Phosphopantetheinyl Hydrolase (PptH) from Mycobacterium tuberculosis
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