2v2c: Difference between revisions

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New page: left|200px<br /><applet load="2v2c" size="350" color="white" frame="true" align="right" spinBox="true" caption="2v2c, resolution 1.89Å" /> '''THE A178L MUTATION I...
 
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[[Image:2v2c.jpg|left|200px]]<br /><applet load="2v2c" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2v2c, resolution 1.89&Aring;" />
'''THE A178L MUTATION IN THE C-TERMINAL HINGE OF THE FLEXIBLE LOOP-6 OF TRIOSEPHOSPHATE ISOMERASE (TIM) INDUCES A MORE CLOSED CONFORMATION OF THIS HINGE REGION IN DIMERIC AND MONOMERIC TIM'''<br />


==Overview==
==The A178L mutation in the C-terminal hinge of the flexible loop-6 of triosephosphate isomerase (TIM) induces a more closed conformation of this hinge region in dimeric and monomeric TIM==
The flexible catalytic loop, loop-6, of TIM has evolved to preferably be open in the unliganded state and to preferably be closed in the liganded state. The N-terminal and C-terminal hinges of this loop are important for its opening/closing mechanism. In this study, a small conserved C-terminal hinge residue, Ala178, has been mutated into a residue with a larger side chain, Leu178. This mutation has been made in the dimeric trypanosomal wild-type TIM (wtTIM) and in its mutated catalytically competent monomeric variant (ml1TIM). The variants are referred to as A178L and ml1A178L, respectively. Crystal structures have been determined of unliganded A178L (at 2.2 A), liganded A178L (at 1.89 A), unliganded ml1A178L (at 2.3 A) and liganded ml1A178L (at 1.18 A) using the transition-state analogue 2-phosphoglycolate as a ligand. Structural characterization of the two variants shows that this mutation favours the closed conformation of the C-terminal hinge region, even in the absence of ligand. In the structure of the unliganded A178L variant a range of new loop-6 conformations are observed, including subunits in which the tip of loop-6 is completely disordered. The catalytic efficiency of A178L is lower than that of wtTIM, which correlates with the structural differences between the apo forms of wtTIM and A178L, in particular the more disordered loop-6 in the structure of unliganded A178L. In the liganded structures of A178L and ml1A178L the structural differences induced by the mutation are minimal. Structural characterization of the ml1A178L variant highlights its structural plasticity.
<StructureSection load='2v2c' size='340' side='right'caption='[[2v2c]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2v2c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V2C 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]] 1.89&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PGA:2-PHOSPHOGLYCOLIC+ACID'>PGA</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=2v2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v2c OCA], [https://pdbe.org/2v2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v2c RCSB], [https://www.ebi.ac.uk/pdbsum/2v2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v2c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TPIS_TRYBB TPIS_TRYBB]
== 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/v2/2v2c_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2v2c ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2V2C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei] with <scene name='pdbligand=PGA:'>PGA</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] Known structural/functional Sites: <scene name='pdbsite=AC1:Binding+Site+For+Residue+So4+A+1251'>AC1</scene>, <scene name='pdbsite=AC2:Binding+Site+For+Residue+So4+A+1252'>AC2</scene>, <scene name='pdbsite=AC3:Binding+Site+For+Residue+So4+A+1253'>AC3</scene> and <scene name='pdbsite=AC4:Binding+Site+For+Residue+Pga+A+1254'>AC4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V2C OCA].
*[[Triose phosphate isomerase 3D structures|Triose phosphate isomerase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Structural studies show that the A178L mutation in the C-terminal hinge of the catalytic loop-6 of triosephosphate isomerase (TIM) induces a closed-like conformation in dimeric and monomeric TIM., Alahuhta M, Casteleijn MG, Neubauer P, Wierenga RK, Acta Crystallogr D Biol Crystallogr. 2008 Feb;64(Pt 2):178-88. Epub 2008, Jan 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18219118 18219118]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Triose-phosphate isomerase]]
[[Category: Trypanosoma brucei brucei]]
[[Category: Trypanosoma brucei brucei]]
[[Category: Alahuhta, M.]]
[[Category: Alahuhta M]]
[[Category: Casteleijn, M G.]]
[[Category: Casteleijn MG]]
[[Category: Neubauer, P.]]
[[Category: Neubauer P]]
[[Category: Wierenga, R K.]]
[[Category: Wierenga RK]]
[[Category: PGA]]
[[Category: SO4]]
[[Category: 2-phospho glycollate]]
[[Category: 2pg]]
[[Category: a178l]]
[[Category: engineering]]
[[Category: enzyme]]
[[Category: fatty acid biosynthesis]]
[[Category: gluconeogenesis]]
[[Category: glycolysis]]
[[Category: glycosome]]
[[Category: hinge]]
[[Category: isomerase]]
[[Category: lipid synthesis]]
[[Category: loop-6]]
[[Category: loop6]]
[[Category: pentose shunt]]
[[Category: point mutation]]
[[Category: tim]]
[[Category: tim-barrel]]
[[Category: triosephosphate isomerase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:52:51 2008''

Latest revision as of 10:06, 1 May 2024

The A178L mutation in the C-terminal hinge of the flexible loop-6 of triosephosphate isomerase (TIM) induces a more closed conformation of this hinge region in dimeric and monomeric TIMThe A178L mutation in the C-terminal hinge of the flexible loop-6 of triosephosphate isomerase (TIM) induces a more closed conformation of this hinge region in dimeric and monomeric TIM

Structural highlights

2v2c is a 1 chain structure with sequence from Trypanosoma brucei brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.89Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TPIS_TRYBB

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2v2c, resolution 1.89Å

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