5hii: Difference between revisions
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==Crystal structure of glycine sarcosine N-methyltransferase (GSMT) from Methanohalophilus portucalensis (apo form)== | |||
<StructureSection load='5hii' size='340' side='right'caption='[[5hii]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5hii]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Methanohalophilus_portucalensis_FDF-1 Methanohalophilus portucalensis FDF-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HII OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HII 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5hii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hii OCA], [https://pdbe.org/5hii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hii RCSB], [https://www.ebi.ac.uk/pdbsum/5hii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hii ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/F6KV61_9EURY F6KV61_9EURY] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Methyltransferases play crucial roles in many cellular processes, and various regulatory mechanisms have evolved to control their activities. For methyltransferases involved in biosynthetic pathways, regulation via feedback inhibition is a commonly employed strategy to prevent excessive accumulation of the pathways' end products. To date, no biosynthetic methyltransferases have been characterized by X-ray crystallography in complex with their corresponding end product. Here, we report the crystal structures of the glycine sarcosine N-methyltransferase from the halophilic archaeon Methanohalophilus portucalensis (MpGSMT), which represents the first structural elucidation of the GSMT methyltransferase family. As the first enzyme in the biosynthetic pathway of the osmoprotectant betaine, MpGSMT catalyzes N-methylation of glycine and sarcosine, and its activity is feedback-inhibited by the end product betaine. A structural analysis revealed that, despite the simultaneous presence of both substrate (sarcosine) and cofactor (S-adenosyl-L-homocysteine; SAH), the enzyme was likely crystallized in an inactive conformation, as additional structural changes are required to complete the active site assembly. Consistent with this interpretation, the bound SAH can be replaced by the methyl donor S-adenosyl-L-methionine without triggering the methylation reaction. Furthermore, the observed conformational state was found to harbor a betaine-binding site, suggesting that betaine may inhibit MpGSMT activity by trapping the enzyme in an inactive form. This work implicates a structural basis by which feedback inhibition of biosynthetic methyltransferases may be achieved. | |||
Structural Analysis of Glycine Sarcosine N-methyltransferase from Methanohalophilus portucalensis Reveals Mechanistic Insights into the Regulation of Methyltransferase Activity.,Lee YR, Lin TS, Lai SJ, Liu MS, Lai MC, Chan NL Sci Rep. 2016 Dec 9;6:38071. doi: 10.1038/srep38071. PMID:27934872<ref>PMID:27934872</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5hii" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Lai | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Lin | [[Category: Large Structures]] | ||
[[Category: Methanohalophilus portucalensis FDF-1]] | |||
[[Category: Chan NL]] | |||
[[Category: Lai MC]] | |||
[[Category: Lai SJ]] | |||
[[Category: Lee YR]] | |||
[[Category: Lin TS]] | |||
[[Category: Liu MS]] | |||
Latest revision as of 10:38, 9 August 2023
Crystal structure of glycine sarcosine N-methyltransferase (GSMT) from Methanohalophilus portucalensis (apo form)Crystal structure of glycine sarcosine N-methyltransferase (GSMT) from Methanohalophilus portucalensis (apo form)
Structural highlights
FunctionPublication Abstract from PubMedMethyltransferases play crucial roles in many cellular processes, and various regulatory mechanisms have evolved to control their activities. For methyltransferases involved in biosynthetic pathways, regulation via feedback inhibition is a commonly employed strategy to prevent excessive accumulation of the pathways' end products. To date, no biosynthetic methyltransferases have been characterized by X-ray crystallography in complex with their corresponding end product. Here, we report the crystal structures of the glycine sarcosine N-methyltransferase from the halophilic archaeon Methanohalophilus portucalensis (MpGSMT), which represents the first structural elucidation of the GSMT methyltransferase family. As the first enzyme in the biosynthetic pathway of the osmoprotectant betaine, MpGSMT catalyzes N-methylation of glycine and sarcosine, and its activity is feedback-inhibited by the end product betaine. A structural analysis revealed that, despite the simultaneous presence of both substrate (sarcosine) and cofactor (S-adenosyl-L-homocysteine; SAH), the enzyme was likely crystallized in an inactive conformation, as additional structural changes are required to complete the active site assembly. Consistent with this interpretation, the bound SAH can be replaced by the methyl donor S-adenosyl-L-methionine without triggering the methylation reaction. Furthermore, the observed conformational state was found to harbor a betaine-binding site, suggesting that betaine may inhibit MpGSMT activity by trapping the enzyme in an inactive form. This work implicates a structural basis by which feedback inhibition of biosynthetic methyltransferases may be achieved. Structural Analysis of Glycine Sarcosine N-methyltransferase from Methanohalophilus portucalensis Reveals Mechanistic Insights into the Regulation of Methyltransferase Activity.,Lee YR, Lin TS, Lai SJ, Liu MS, Lai MC, Chan NL Sci Rep. 2016 Dec 9;6:38071. doi: 10.1038/srep38071. PMID:27934872[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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