View source for 4pfn


==Crystal structure of Plasmodium vivax SHMT with L-serine Schiff base==
<StructureSection load='4pfn' size='340' side='right'caption='[[4pfn]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pfn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax_Sal-1 Plasmodium vivax Sal-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PFN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PFN 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SER:SERINE'>SER</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=4pfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pfn OCA], [https://pdbe.org/4pfn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pfn RCSB], [https://www.ebi.ac.uk/pdbsum/4pfn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pfn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A5K8L9_PLAVS A5K8L9_PLAVS] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Plasmodium parasites, the causative agent of malaria, rely heavily on de novo folate biosynthesis, and the enzymes in this pathway have therefore been explored extensively for antimalarial development. Serine hydroxymethyltransferase (SHMT) from Plasmodium spp., an enzyme involved in folate recycling and dTMP synthesis, has been shown to catalyze the conversion of L- and D-serine to glycine (Gly) in a THF-dependent reaction, the mechanism of which is not yet fully understood. Here, the crystal structures of P. vivax SHMT (PvSHMT) in a binary complex with L-serine and in a ternary complex with D-serine (D-Ser) and (6R)-5-formyltetrahydrofolate (5FTHF) provide clues to the mechanism underlying the control of enzyme activity. 5FTHF in the ternary-complex structure was found in the 6R form, thus differing from the previously reported structures of SHMT-Gly-(6S)-5FTHF from other organisms. This suggested that the presence of D-Ser in the active site can alter the folate-binding specificity. Investigation of binding in the presence of D-Ser and the (6R)- or (6S)-5FTHF enantiomers indicated that both forms of 5FTHF can bind to the enzyme but that only (6S)-5FTHF gives rise to a quinonoid intermediate. Likewise, a large surface area with a highly positively charged electrostatic potential surrounding the PvSHMT folate pocket suggested a preference for a polyglutamated folate substrate similar to the mammalian SHMTs. Furthermore, as in P. falciparum SHMT, a redox switch created from a cysteine pair (Cys125-Cys364) was observed. Overall, these results assert the importance of features such as stereoselectivity and redox status for control of the activity and specificity of PvSHMT.

Structures of Plasmodium vivax serine hydroxymethyltransferase: implications for ligand-binding specificity and functional control.,Chitnumsub P, Jaruwat A, Riangrungroj P, Ittarat W, Noytanom K, Oonanant W, Vanichthanankul J, Chuankhayan P, Maenpuen S, Chen CJ, Chaiyen P, Yuthavong Y, Leartsakulpanich U Acta Crystallogr D Biol Crystallogr. 2014 Dec 1;70(Pt 12):3177-86. doi:, 10.1107/S1399004714023128. Epub 2014 Nov 22. PMID:25478836<ref>PMID:25478836</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4pfn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium vivax Sal-1]]
[[Category: Chitnumsub P]]
[[Category: Jaruwat A]]
[[Category: Leartsakulpanich U]]