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| | ==Mycobacterium tuberculosis SuhB== | | ==Mycobacterium tuberculosis SuhB== |
| - | <StructureSection load='2q74' size='340' side='right' caption='[[2q74]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='2q74' size='340' side='right'caption='[[2q74]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2q74]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q74 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q74 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2q74]] is a 3 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=2Q74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q74 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">suhB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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]] 2.6Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Inositol-phosphate_phosphatase Inositol-phosphate phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.25 3.1.3.25] </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=2q74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q74 OCA], [https://pdbe.org/2q74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q74 RCSB], [https://www.ebi.ac.uk/pdbsum/2q74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q74 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q74 OCA], [http://pdbe.org/2q74 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q74 RCSB], [http://www.ebi.ac.uk/pdbsum/2q74 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SUHB_MYCTU SUHB_MYCTU]] Catalyzes the dephosphorylation of inositol 1-phosphate (I-1-P) to yield free myo-inositol, a key metabolite in mycobacteria. Is also able to hydrolyze a variety of polyol phosphates such as glucitol-6-phosphate, inositol 2-phosphate (I-2-P), glycerol-2-phosphate, and 2'-AMP, albeit with reduced efficiency.<ref>PMID:11914086</ref> | + | [https://www.uniprot.org/uniprot/SUHB_MYCTU SUHB_MYCTU] Catalyzes the dephosphorylation of inositol 1-phosphate (I-1-P) to yield free myo-inositol, a key metabolite in mycobacteria. Is also able to hydrolyze a variety of polyol phosphates such as glucitol-6-phosphate, inositol 2-phosphate (I-2-P), glycerol-2-phosphate, and 2'-AMP, albeit with reduced efficiency.<ref>PMID:11914086</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q7/2q74_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q7/2q74_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | ==See Also== | | ==See Also== |
| - | *[[Inositol Monophosphatase|Inositol Monophosphatase]] | + | *[[Inositol monophosphatase 3D structures|Inositol monophosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Inositol-phosphate phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Besra, G S]] | + | [[Category: Besra GS]] |
| - | [[Category: Brown, A K]] | + | [[Category: Brown AK]] |
| - | [[Category: Futterer, K]] | + | [[Category: Futterer K]] |
| - | [[Category: Ghadbane, H]] | + | [[Category: Ghadbane H]] |
| - | [[Category: Meng, G]] | + | [[Category: Meng G]] |
| - | [[Category: Alpha-beta-alpha-beta-alpha sandwich]]
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| - | [[Category: Hydrolase]]
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| Structural highlights
Function
SUHB_MYCTU Catalyzes the dephosphorylation of inositol 1-phosphate (I-1-P) to yield free myo-inositol, a key metabolite in mycobacteria. Is also able to hydrolyze a variety of polyol phosphates such as glucitol-6-phosphate, inositol 2-phosphate (I-2-P), glycerol-2-phosphate, and 2'-AMP, albeit with reduced efficiency.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase). Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. RESULTS: We determined the crystal structure, to 2.6 A resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. CONCLUSION: The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity.
Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+.,Brown AK, Meng G, Ghadbane H, Scott DJ, Dover LG, Nigou J, Besra GS, Futterer K BMC Struct Biol. 2007 Aug 28;7:55. PMID:17725819[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nigou J, Dover LG, Besra GS. Purification and biochemical characterization of Mycobacterium tuberculosis SuhB, an inositol monophosphatase involved in inositol biosynthesis. Biochemistry. 2002 Apr 2;41(13):4392-8. PMID:11914086
- ↑ Brown AK, Meng G, Ghadbane H, Scott DJ, Dover LG, Nigou J, Besra GS, Futterer K. Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+. BMC Struct Biol. 2007 Aug 28;7:55. PMID:17725819 doi:10.1186/1472-6807-7-55
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