9j4h
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of SHMT apo form== | |
| + | <StructureSection load='9j4h' size='340' side='right'caption='[[9j4h]], [[Resolution|resolution]] 2.04Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9j4h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9J4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9J4H 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]] 2.04Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=9j4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9j4h OCA], [https://pdbe.org/9j4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9j4h RCSB], [https://www.ebi.ac.uk/pdbsum/9j4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9j4h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A133CK16_ENTFC A0A133CK16_ENTFC] 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.[HAMAP-Rule:MF_00051] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Novel classes of antibiotics are needed to improve the resilience of the healthcare system to antimicrobial resistance (AMR), including vancomycin resistance. vanA gene cluster is a cause of vancomycin resistance. This gene cluster is transferred and spreads vancomycin resistance from Enterococcus spp. to Staphylococcus aureus. Therefore, novel antibacterial agents are required to combat AMR, including vanA-type vancomycin resistance. Serine hydroxymethyltransferase (SHMT) is a key target of antibacterial agents. However, the specific binding mechanisms of SHMT inhibitors remain unclear. Detailed structural information will contribute to understanding these mechanisms. In this study, we found that (+)-SHIN-2, the first in vivo active inhibitor of human SHMT, is strongly bound to the Enterococcus faecium SHMT (efmSHMT). Comparison of the crystal structures of apo- and (+)-SHIN-2-boud efmSHMT revealed that (+)-SHIN-2 stabilized the active site loop of efmSHMT via hydrogen bonds, which are critical for efmSHMT inhibition. Additionally, (+)-SHIN-2 formed hydrogen bonds with serine, forming the Schiff's base with pyridoxal 5'-phosphate, which is a co-factor of SHMT. Furthermore, (+)-SHIN-2 exerted biostatic effects on vancomycin-susceptible and vanA-type vancomycin-resistant E. faecium in vitro, indicating that SHMT inhibitors do not induce cross-resistance to vanA-type vancomycin. Overall, these findings can aid in the design of novel SHMT inhibitors to combat AMR, including vancomycin resistance. | ||
| - | + | SHIN-2 exerts potent activity against VanA-type vancomycin-resistant Enterococcus faecium in vitro by stabilizing the active site loop of serine hydroxymethyltransferase.,Hayashi H, Saijo E, Hirata K, Murakami S, Okuda H, Kodama EN, Hasegawa K, Murayama K Arch Biochem Biophys. 2024 Sep 21;761:110160. doi: 10.1016/j.abb.2024.110160. PMID:39313141<ref>PMID:39313141</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Hayashi | + | <div class="pdbe-citations 9j4h" style="background-color:#fffaf0;"></div> |
| - | [[Category: Murayama | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Enterococcus faecium]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hayashi H]] | ||
| + | [[Category: Murayama K]] | ||
Current revision
Crystal structure of SHMT apo form
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