|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6wyn' size='340' side='right'caption='[[6wyn]], [[Resolution|resolution]] 1.81Å' scene=''> | | <StructureSection load='6wyn' size='340' side='right'caption='[[6wyn]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wyn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wyn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYN FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.81Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6wym|6wym]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rv0045c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=6wyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyn OCA], [https://pdbe.org/6wyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyn RCSB], [https://www.ebi.ac.uk/pdbsum/6wyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyn ProSAT]</span></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=6wyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyn OCA], [https://pdbe.org/6wyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyn RCSB], [https://www.ebi.ac.uk/pdbsum/6wyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/EST45_MYCTU EST45_MYCTU]] Esterase likely involved in ester/lipid metabolism. Shows strong substrate selectivity toward short, straight chain alkyl esters with the highest activity toward four atom chains. The physiological substrate is unknown (PubMed:25354081). Is able to hydrolyze ester bonds within a wide range of p-nitrophenyl derivatives (C2-C14) in vitro (PubMed:20957207).<ref>PMID:20957207</ref> <ref>PMID:25354081</ref>
| + | [https://www.uniprot.org/uniprot/EST45_MYCTU EST45_MYCTU] Esterase likely involved in ester/lipid metabolism. Shows strong substrate selectivity toward short, straight chain alkyl esters with the highest activity toward four atom chains. The physiological substrate is unknown (PubMed:25354081). Is able to hydrolyze ester bonds within a wide range of p-nitrophenyl derivatives (C2-C14) in vitro (PubMed:20957207).<ref>PMID:20957207</ref> <ref>PMID:25354081</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 24: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Hoops, G C]] | + | [[Category: Hoops GC]] |
| - | [[Category: Johnson, R J]] | + | [[Category: Johnson RJ]] |
| - | [[Category: Macbeth, M R]] | + | [[Category: Macbeth MR]] |
| - | [[Category: Allosteric regulation]]
| + | |
| - | [[Category: Conformational change]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Serine esterase]]
| + | |
| Structural highlights
Function
EST45_MYCTU Esterase likely involved in ester/lipid metabolism. Shows strong substrate selectivity toward short, straight chain alkyl esters with the highest activity toward four atom chains. The physiological substrate is unknown (PubMed:25354081). Is able to hydrolyze ester bonds within a wide range of p-nitrophenyl derivatives (C2-C14) in vitro (PubMed:20957207).[1] [2]
Publication Abstract from PubMed
Mycobacterium tuberculosis virulence is highly metal-dependent with metal availability modulating the shift from the dormant to active states of M. tuberculosis infection. Rv0045c from M. tuberculosis is a proposed metabolic serine hydrolase whose folded stability is dependent on divalent metal concentration. Herein, we measured the divalent metal inhibition profile of the enzymatic activity of Rv0045c and found specific divalent transition metal cations (Cu(2+) >/= Zn(2+) > Ni(2+) > Co(2+) ) strongly inhibited its enzymatic activity. The metal cations bind allosterically, largely affecting values for kcat rather than KM . Removal of the artificial N-terminal 6xHis-tag did not change the metal-dependent inhibition, indicating that the allosteric inhibition site is native to Rv0045c. To isolate the site of this allosteric regulation in Rv0045c, the structures of Rv0045c were determined at 1.8 a and 2.0 a resolution in the presence and absence of Zn(2+) with each structure containing a previously unresolved dynamic loop spanning the binding pocket. Through the combination of structural analysis with and without zinc and targeted mutagenesis, this metal-dependent inhibition was traced to multiple chelating residues (H202A/E204A) on a flexible loop, suggesting dynamic allosteric regulation of Rv0045c by divalent metals. Although serine hydrolases like Rv0045c are a large and diverse enzyme superfamily, this is the first structural confirmation of allosteric regulation of their enzymatic activity by divalent metals. This article is protected by copyright. All rights reserved.
Transition metal cation inhibition of Mycobacterium tuberculosis esterase RV0045C.,Bowles IE, Pool EH, Lancaster BS, Lawson EK, Savas CP, Kartje ZJ, Severinac L, Cho DH, Macbeth MR, Johnson RJ, Hoops GC Protein Sci. 2021 Apr 29. doi: 10.1002/pro.4089. PMID:33914998[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Guo J, Zheng X, Xu L, Liu Z, Xu K, Li S, Wen T, Liu S, Pang H. Characterization of a novel esterase Rv0045c from Mycobacterium tuberculosis. PLoS One. 2010 Oct 1;5(10). doi: 10.1371/journal.pone.0013143. PMID:20957207 doi:http://dx.doi.org/10.1371/journal.pone.0013143
- ↑ Lukowski JK, Savas CP, Gehring AM, McKary MG, Adkins CT, Lavis LD, Hoops GC, Johnson RJ. Distinct substrate selectivity of a metabolic hydrolase from Mycobacterium tuberculosis. Biochemistry. 2014 Dec 2;53(47):7386-95. doi: 10.1021/bi501108u. Epub 2014 Nov, 17. PMID:25354081 doi:http://dx.doi.org/10.1021/bi501108u
- ↑ Bowles IE, Pool EH, Lancaster BS, Lawson EK, Savas CP, Kartje ZJ, Severinac L, Cho DH, Macbeth MR, Johnson RJ, Hoops GC. Transition metal cation inhibition of Mycobacterium tuberculosis esterase RV0045C. Protein Sci. 2021 Apr 29. doi: 10.1002/pro.4089. PMID:33914998 doi:http://dx.doi.org/10.1002/pro.4089
|
