2b7o: Difference between revisions
Jump to navigation
Jump to search
New page: left|200px<br /><applet load="2b7o" size="350" color="white" frame="true" align="right" spinBox="true" caption="2b7o, resolution 2.30Å" /> '''The Structure of 3-D... |
No edit summary |
||
| (16 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==The Structure of 3-Deoxy-D-Arabino-Heptulosonate 7-Phosphate Synthase from Mycobacterium tuberculosis== | ||
The shikimate pathway, responsible for the biosynthesis of aromatic | <StructureSection load='2b7o' size='340' side='right'caption='[[2b7o]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2b7o]] is a 2 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=2B7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B7O 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CE1:O-DODECANYL+OCTAETHYLENE+GLYCOL'>CE1</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PEP:PHOSPHOENOLPYRUVATE'>PEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2b7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b7o OCA], [https://pdbe.org/2b7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b7o RCSB], [https://www.ebi.ac.uk/pdbsum/2b7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b7o ProSAT], [https://www.topsan.org/Proteins/TBSGC/2b7o TOPSAN]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AROG_MYCTU AROG_MYCTU] Catalyzes an aldol-like condensation reaction between phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P) to generate 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) and inorganic phosphate.<ref>PMID:16288916</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b7/2b7o_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2b7o ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The shikimate pathway, responsible for the biosynthesis of aromatic compounds, is essential for the growth of Mycobacterium tuberculosis and is a potential target for the design of new anti-tuberculosis drugs. The first step of this pathway is catalyzed by 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS). The DAH7PSs have been classified into two apparently unrelated types and, whereas structural data have been obtained for the type I DAH7PSs, no structural information is available for their type II counterparts. The type II DAH7PS from M.tuberculosis has been expressed in Escherichia coli, purified, functionally characterized and crystallized. It is found to be metal ion-dependent and subject to feedback inhibition by phenylalanine, tryptophan, tyrosine and chorismate, with a significant synergistic effect when tryptophan is used in combination with phenylalanine. The crystal structure of M.tuberculosis DAH7PS has been determined by single-wavelength anomalous diffraction and refined at 2.3A in complex with substrate phosphoenolpyruvate and Mn(2+). The structure reveals a tightly associated dimer of (beta/alpha)(8) TIM barrels. The monomer fold, the arrangement of key residues in the active site, and the binding modes of PEP and Mn(2+), all match those of the type I enzymes, and indicate a common ancestry for the type I and type II DAH7PSs, despite their minimal sequence identity. In contrast, the structural elements that decorate the core (beta/alpha)(8) fold differ from those in the type I enzymes, consistent with their different regulatory and oligomeric properties. | |||
The structure of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis reveals a common catalytic scaffold and ancestry for type I and type II enzymes.,Webby CJ, Baker HM, Lott JS, Baker EN, Parker EJ J Mol Biol. 2005 Dec 9;354(4):927-39. Epub 2005 Oct 21. PMID:16288916<ref>PMID:16288916</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2b7o" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DAHP synthase 3D structures|DAHP synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis H37Rv]] | |||
[[Category: Baker EN]] | |||
[[Category: Baker HM]] | |||
[[Category: Lott JS]] | |||
[[Category: Parker EJ]] | |||
[[Category: Webby CJ]] | |||
Latest revision as of 08:06, 17 October 2024
The Structure of 3-Deoxy-D-Arabino-Heptulosonate 7-Phosphate Synthase from Mycobacterium tuberculosisThe Structure of 3-Deoxy-D-Arabino-Heptulosonate 7-Phosphate Synthase from Mycobacterium tuberculosis
Structural highlights
FunctionAROG_MYCTU Catalyzes an aldol-like condensation reaction between phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P) to generate 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) and inorganic phosphate.[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 PubMedThe shikimate pathway, responsible for the biosynthesis of aromatic compounds, is essential for the growth of Mycobacterium tuberculosis and is a potential target for the design of new anti-tuberculosis drugs. The first step of this pathway is catalyzed by 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS). The DAH7PSs have been classified into two apparently unrelated types and, whereas structural data have been obtained for the type I DAH7PSs, no structural information is available for their type II counterparts. The type II DAH7PS from M.tuberculosis has been expressed in Escherichia coli, purified, functionally characterized and crystallized. It is found to be metal ion-dependent and subject to feedback inhibition by phenylalanine, tryptophan, tyrosine and chorismate, with a significant synergistic effect when tryptophan is used in combination with phenylalanine. The crystal structure of M.tuberculosis DAH7PS has been determined by single-wavelength anomalous diffraction and refined at 2.3A in complex with substrate phosphoenolpyruvate and Mn(2+). The structure reveals a tightly associated dimer of (beta/alpha)(8) TIM barrels. The monomer fold, the arrangement of key residues in the active site, and the binding modes of PEP and Mn(2+), all match those of the type I enzymes, and indicate a common ancestry for the type I and type II DAH7PSs, despite their minimal sequence identity. In contrast, the structural elements that decorate the core (beta/alpha)(8) fold differ from those in the type I enzymes, consistent with their different regulatory and oligomeric properties. The structure of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis reveals a common catalytic scaffold and ancestry for type I and type II enzymes.,Webby CJ, Baker HM, Lott JS, Baker EN, Parker EJ J Mol Biol. 2005 Dec 9;354(4):927-39. Epub 2005 Oct 21. PMID:16288916[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||