5mi7: Difference between revisions
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==BtGH84 mutant with covalent modification by MA4 in complex with PUGNAc== | |||
<StructureSection load='5mi7' size='340' side='right'caption='[[5mi7]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5mi7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MI7 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7NT:~{N}-(4-morpholin-4-ylthieno[2,3-d]pyrimidin-2-yl)propanamide'>7NT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=OAN:O-(2-ACETAMIDO-2-DEOXY+D-GLUCOPYRANOSYLIDENE)+AMINO-N-PHENYLCARBAMATE'>OAN</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=5mi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mi7 OCA], [https://pdbe.org/5mi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mi7 RCSB], [https://www.ebi.ac.uk/pdbsum/5mi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mi7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/OGA_BACTN OGA_BACTN] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Modulation of enzyme activity is a powerful means of probing cellular function and can be exploited for diverse applications. Here, we explore a method of enzyme activation where covalent tethering of a small molecule to an enzyme can increase catalytic activity (kcat/KM) up to 35-fold. Using a bacterial glycoside hydrolase, BtGH84, we demonstrate how small molecule "fragments", identified as activators in free solution, can be covalently tethered to the protein using Michael-addition chemistry. We show how tethering generates a constitutively-activated enzyme-fragment conjugate, which displays both improved catalytic efficiency and increased susceptibility to certain inhibitor classes. Structure guided modifications of the tethered fragment demonstrate how specific interactions between the fragment and the enzyme influence the extent of activation. This work suggests that a similar approach may be used to modulate the activity of enzymes such as to improve catalytic efficiency or increase inhibitor susceptibility. | |||
Increase of enzyme activity through specific covalent modification with fragments.,Darby JF, Atobe M, Firth JD, Bond P, Davies GJ, O'Brien P, Hubbard RE Chem Sci. 2017 Nov 1;8(11):7772-7779. doi: 10.1039/c7sc01966a. Epub 2017 Sep 27. PMID:29163914<ref>PMID:29163914</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5mi7" style="background-color:#fffaf0;"></div> | ||
[[Category: Davies | |||
[[Category: | ==See Also== | ||
*[[O-GlcNAcase|O-GlcNAcase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacteroides thetaiotaomicron VPI-5482]] | |||
[[Category: Large Structures]] | |||
[[Category: Darby JF]] | |||
[[Category: Davies GJ]] | |||
[[Category: Hubbard RE]] | |||
Latest revision as of 21:44, 1 November 2023
BtGH84 mutant with covalent modification by MA4 in complex with PUGNAcBtGH84 mutant with covalent modification by MA4 in complex with PUGNAc
Structural highlights
FunctionOGA_BACTN Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Publication Abstract from PubMedModulation of enzyme activity is a powerful means of probing cellular function and can be exploited for diverse applications. Here, we explore a method of enzyme activation where covalent tethering of a small molecule to an enzyme can increase catalytic activity (kcat/KM) up to 35-fold. Using a bacterial glycoside hydrolase, BtGH84, we demonstrate how small molecule "fragments", identified as activators in free solution, can be covalently tethered to the protein using Michael-addition chemistry. We show how tethering generates a constitutively-activated enzyme-fragment conjugate, which displays both improved catalytic efficiency and increased susceptibility to certain inhibitor classes. Structure guided modifications of the tethered fragment demonstrate how specific interactions between the fragment and the enzyme influence the extent of activation. This work suggests that a similar approach may be used to modulate the activity of enzymes such as to improve catalytic efficiency or increase inhibitor susceptibility. Increase of enzyme activity through specific covalent modification with fragments.,Darby JF, Atobe M, Firth JD, Bond P, Davies GJ, O'Brien P, Hubbard RE Chem Sci. 2017 Nov 1;8(11):7772-7779. doi: 10.1039/c7sc01966a. Epub 2017 Sep 27. PMID:29163914[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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