1m7o: Difference between revisions
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==Plasmodium Falciparum Triosephosphate isomerase (PfTIM) compled to substrate analog 3-phosphoglycerate (3PG)== | |||
<StructureSection load='1m7o' size='340' side='right' caption='[[1m7o]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1m7o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M7O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M7O FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PG:3-PHOSPHOGLYCERIC+ACID'>3PG</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ydv|1ydv]], [[1lzo|1lzo]], [[1lyx|1lyx]], [[1m7p|1m7p]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m7o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1m7o RCSB], [http://www.ebi.ac.uk/pdbsum/1m7o PDBsum]</span></td></tr> | |||
<table> | |||
== 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/m7/1m7o_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The glycolytic enzymes of Plasmodium falciparum (Pf) are attractive drug targets as the parasites lack a functional tricarboxylic cycle and hence depend heavily on glycolysis for their energy requirements. Structural comparisons between Pf triosephosphate isomerase (PfTIM) and its human homologue have highlighted the important differences between the host and parasite enzymes [Velanker et al. (1997), Structure, 5, 751-761]. Structures of various PfTIM-ligand complexes have been determined in order to gain further insight into the mode of inhibitor binding to the parasite enzyme. Structures of two PfTIM-substrate analogue complexes, those of 3-phosphoglycerate (3PG) and glycerol-3-phosphate (G3P), have been determined and refined at 2.4 A resolution. Both complexes crystallized in the monoclinic space group P2(1), with a molecular dimer in the asymmetric unit. The novel aspect of these structures is the adoption of the 'loop-open' conformation, with the catalytic loop (loop 6, residues 166-176) positioned away from the active site; this loop is known to move by about 7 A towards the active site upon inhibitor binding in other TIMs. The loop-open form in the PfTIM complexes appears to be a consequence of the S96F mutation, which is specific to the enzymes from malarial parasites. Structural comparison with the corresponding complexes of Trypanosoma brucei TIM (TrypTIM) shows that extensive steric clashes may be anticipated between Phe96 and Ile172 in the 'closed' conformation of the catalytic loop, preventing loop closure in PfTIM. Ser73 in PfTIM (Ala in all other known TIMs) appears to provide an anchoring water-mediated hydrogen bond to the ligand, compensating for the loss of a stabilizing hydrogen bond from Gly171 NH in the closed-loop liganded TIM structures. | |||
Structures of Plasmodium falciparum triosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state.,Parthasarathy S, Balaram H, Balaram P, Murthy MR Acta Crystallogr D Biol Crystallogr. 2002 Dec;58(Pt 12):1992-2000. Epub, 2002 Nov 23. PMID:12454456<ref>PMID:12454456</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Triose Phosphate Isomerase|Triose Phosphate Isomerase]] | *[[Triose Phosphate Isomerase|Triose Phosphate Isomerase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
[[Category: Triose-phosphate isomerase]] | [[Category: Triose-phosphate isomerase]] | ||
Revision as of 20:22, 29 September 2014
Plasmodium Falciparum Triosephosphate isomerase (PfTIM) compled to substrate analog 3-phosphoglycerate (3PG)Plasmodium Falciparum Triosephosphate isomerase (PfTIM) compled to substrate analog 3-phosphoglycerate (3PG)
Structural highlights
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 glycolytic enzymes of Plasmodium falciparum (Pf) are attractive drug targets as the parasites lack a functional tricarboxylic cycle and hence depend heavily on glycolysis for their energy requirements. Structural comparisons between Pf triosephosphate isomerase (PfTIM) and its human homologue have highlighted the important differences between the host and parasite enzymes [Velanker et al. (1997), Structure, 5, 751-761]. Structures of various PfTIM-ligand complexes have been determined in order to gain further insight into the mode of inhibitor binding to the parasite enzyme. Structures of two PfTIM-substrate analogue complexes, those of 3-phosphoglycerate (3PG) and glycerol-3-phosphate (G3P), have been determined and refined at 2.4 A resolution. Both complexes crystallized in the monoclinic space group P2(1), with a molecular dimer in the asymmetric unit. The novel aspect of these structures is the adoption of the 'loop-open' conformation, with the catalytic loop (loop 6, residues 166-176) positioned away from the active site; this loop is known to move by about 7 A towards the active site upon inhibitor binding in other TIMs. The loop-open form in the PfTIM complexes appears to be a consequence of the S96F mutation, which is specific to the enzymes from malarial parasites. Structural comparison with the corresponding complexes of Trypanosoma brucei TIM (TrypTIM) shows that extensive steric clashes may be anticipated between Phe96 and Ile172 in the 'closed' conformation of the catalytic loop, preventing loop closure in PfTIM. Ser73 in PfTIM (Ala in all other known TIMs) appears to provide an anchoring water-mediated hydrogen bond to the ligand, compensating for the loss of a stabilizing hydrogen bond from Gly171 NH in the closed-loop liganded TIM structures. Structures of Plasmodium falciparum triosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state.,Parthasarathy S, Balaram H, Balaram P, Murthy MR Acta Crystallogr D Biol Crystallogr. 2002 Dec;58(Pt 12):1992-2000. Epub, 2002 Nov 23. PMID:12454456[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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