|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4o6z' size='340' side='right'caption='[[4o6z]], [[Resolution|resolution]] 2.98Å' scene=''> | | <StructureSection load='4o6z' size='340' side='right'caption='[[4o6z]], [[Resolution|resolution]] 2.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4o6z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O6Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O6Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4o6z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O6Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O6Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFL1720w, SHMT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=4o6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6z OCA], [https://pdbe.org/4o6z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o6z RCSB], [https://www.ebi.ac.uk/pdbsum/4o6z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o6z ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycine_hydroxymethyltransferase Glycine hydroxymethyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.1 2.1.2.1] </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=4o6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6z OCA], [http://pdbe.org/4o6z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o6z RCSB], [http://www.ebi.ac.uk/pdbsum/4o6z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o6z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GLYA_PLAF7 GLYA_PLAF7] Catalyzes the interconversion of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, a source of one-carbon units used by thymidylate synthase to convert dUMP to dTMP for DNA synthesis (PubMed:11071283, PubMed:19591883, PubMed:24914963). Binds to its own mRNA and to the mRNA of bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) in vitro; the physiological relevance of this interaction is not clear (PubMed:19591883).<ref>PMID:11071283</ref> <ref>PMID:19591883</ref> <ref>PMID:24914963</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 20: |
Line 20: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Serine hydroxymethyltransferase|Serine hydroxymethyltransferase]] | + | *[[Serine hydroxymethyltransferase 3D structures|Serine hydroxymethyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glycine hydroxymethyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plaf7]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Chitnumsub, P]] | + | [[Category: Chitnumsub P]] |
| - | [[Category: Jaruwat, A]] | + | [[Category: Jaruwat A]] |
| - | [[Category: Leartsakulpanich, U]] | + | [[Category: Leartsakulpanich U]] |
| - | [[Category: Alpha/beta protein]]
| + | |
| - | [[Category: Cytosol]]
| + | |
| - | [[Category: Methyltransferase activity]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
GLYA_PLAF7 Catalyzes the interconversion of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, a source of one-carbon units used by thymidylate synthase to convert dUMP to dTMP for DNA synthesis (PubMed:11071283, PubMed:19591883, PubMed:24914963). Binds to its own mRNA and to the mRNA of bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) in vitro; the physiological relevance of this interaction is not clear (PubMed:19591883).[1] [2] [3]
Publication Abstract from PubMed
Plasmodium falciparum serine hydroxymethyltransferase (PfSHMT), an enzyme in the dTMP synthesis cycle, is an antimalarial target because inhibition of its expression or function has been shown to be lethal to the parasite. As the wild-type enzyme could not be crystallized, protein engineering of residues on the surface was carried out. The surface-engineered mutant PfSHMT-F292E was successfully crystallized and its structure was determined at 3 A resolution. The PfSHMT-F292E structure is a good representation of PfSHMT as this variant revealed biochemical properties similar to those of the wild type. Although the overall structure of PfSHMT is similar to those of other SHMTs, unique features including the presence of two loops and a distinctive cysteine pair formed by Cys125 and Cys364 in the tetrahydrofolate (THF) substrate binding pocket were identified. These structural characteristics have never been reported in other SHMTs. Biochemical characterization and mutation analysis of these two residues confirm that they act as a disulfide/sulfhydryl switch to regulate the THF-dependent catalytic function of the enzyme. This redox switch is not present in the human enzyme, in which the cysteine pair is absent. The data reported here can be further exploited as a new strategy to specifically disrupt the activity of the parasite enzyme without interfering with the function of the human enzyme.
The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities.,Chitnumsub P, Ittarat W, Jaruwat A, Noytanom K, Amornwatcharapong W, Pornthanakasem W, Chaiyen P, Yuthavong Y, Leartsakulpanich U Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1517-27. doi:, 10.1107/S1399004714005598. Epub 2014 May 23. PMID:24914963[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Alfadhli S, Rathod PK. Gene organization of a Plasmodium falciparum serine hydroxymethyltransferase and its functional expression in Escherichia coli. Mol Biochem Parasitol. 2000 Oct;110(2):283-91. doi: , 10.1016/s0166-6851(00)00282-6. PMID:11071283 doi:http://dx.doi.org/10.1016/s0166-6851(00)00282-6
- ↑ Pang CK, Hunter JH, Gujjar R, Podutoori R, Bowman J, Mudeppa DG, Rathod PK. Catalytic and ligand-binding characteristics of Plasmodium falciparum serine hydroxymethyltransferase. Mol Biochem Parasitol. 2009 Nov;168(1):74-83. doi: , 10.1016/j.molbiopara.2009.06.011. Epub 2009 Jul 8. PMID:19591883 doi:http://dx.doi.org/10.1016/j.molbiopara.2009.06.011
- ↑ Chitnumsub P, Ittarat W, Jaruwat A, Noytanom K, Amornwatcharapong W, Pornthanakasem W, Chaiyen P, Yuthavong Y, Leartsakulpanich U. The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities. Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1517-27. doi:, 10.1107/S1399004714005598. Epub 2014 May 23. PMID:24914963 doi:http://dx.doi.org/10.1107/S1399004714005598
- ↑ Chitnumsub P, Ittarat W, Jaruwat A, Noytanom K, Amornwatcharapong W, Pornthanakasem W, Chaiyen P, Yuthavong Y, Leartsakulpanich U. The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities. Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1517-27. doi:, 10.1107/S1399004714005598. Epub 2014 May 23. PMID:24914963 doi:http://dx.doi.org/10.1107/S1399004714005598
|
