View source for 6f93


==Helicobacter pylori serine hydroxymethyl transferase in apo form==
<StructureSection load='6f93' size='340' side='right' caption='[[6f93]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6f93]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F93 FirstGlance]. <br>
</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=6f93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f93 OCA], [http://pdbe.org/6f93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f93 RCSB], [http://www.ebi.ac.uk/pdbsum/6f93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f93 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/GLYA_HELPY GLYA_HELPY]] Catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier. This reaction serves as the major source of one-carbon groups required for the biosynthesis of purines, thymidylate, methionine, and other important biomolecules. Also exhibits THF-independent aldolase activity toward beta-hydroxyamino acids, producing glycine and aldehydes, via a retro-aldol mechanism. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Serine hydroxymethyltransferase (SHMT), encoded by the glyA gene, is a ubiquitous pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the formation of glycine from serine. The thereby generated 5,10-methylene tetrahydrofolate (MTHF) is a major source of cellular one-carbon units and a key intermediate in thymidylate biosynthesis. While in virtually all eukaryotic and many bacterial systems thymidylate synthase ThyA, SHMT and dihydrofolate reductase (DHFR) are part of the thymidylate/folate cycle, the situation is different in organisms using flavin-dependent thymidylate synthase ThyX. Here the distinct catalytic reaction directly produces tetrahydrofolate (THF) and consequently in most ThyX-containing organisms, DHFR is absent. While the resulting influence on the folate metabolism of ThyX-containing bacteria is not fully understood, the presence of ThyX may provide growth benefits under conditions where the level of reduced folate derivatives is compromised. Interestingly, the third key enzyme implicated in generation of MTHF, serine hydroxymethyltransferase (SHMT), has a universal phylogenetic distribution, but remains understudied in ThyX-containg bacteria. To obtain functional insight into these ThyX-dependent thymidylate/folate cycles, we characterized the predicted SHMT from the ThyX-containing bacterium Helicobacter pylori. Serine hydroxymethyltransferase activity was confirmed by functional genetic complementation of a glyA-inactivated E. coli strain. A H. pylori DeltaglyA strain was obtained, but exhibited markedly slowed growth and had lost the virulence factor CagA. Biochemical and spectroscopic evidence indicated formation of a characteristic enzyme-PLP-glycine-folate complex and revealed unexpectedly weak binding affinity of PLP. The three-dimensional structure of the H. pylori SHMT apoprotein was determined at 2.8A resolution, suggesting a structural basis for the low affinity of the enzyme for its cofactor. Stabilization of the proposed inactive configuration using small molecules has potential to provide a specific way for inhibiting HpSHMT.

Structural and functional insight into serine hydroxymethyltransferase from Helicobacter pylori.,Sodolescu A, Dian C, Terradot L, Bouzhir-Sima L, Lestini R, Myllykallio H, Skouloubris S, Liebl U PLoS One. 2018 Dec 14;13(12):e0208850. doi: 10.1371/journal.pone.0208850., eCollection 2018. PMID:30550583<ref>PMID:30550583</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6f93" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Glycine hydroxymethyltransferase]]
[[Category: Bouzhir-Sima, L]]
[[Category: Dian, C]]
[[Category: Lestini, R]]
[[Category: Liebl, U]]
[[Category: Myllykallio, H]]
[[Category: Skouloubris, S]]
[[Category: Sodolescu, A]]
[[Category: Terradot, L]]
[[Category: Folate cycle]]
[[Category: H. pylori folate-sensitive fragile site]]
[[Category: Methyltransferase]]
[[Category: Shmt]]
[[Category: Transferase]]