|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| - | ==BTGH84 IN COMPLEX WITH N-ACETYL GLUCONOLACTAM== | + | ==BtGH84 in complex with N-acetyl gluconolactam== |
| - | <StructureSection load='2xm1' size='340' side='right' caption='[[2xm1]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='2xm1' size='340' side='right'caption='[[2xm1]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xm1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bactn Bactn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XM1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XM1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2xm1]] is a 2 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=2XM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XM1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LTM:N-ACETYL+GLUCONOLACTAM'>LTM</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vvn|2vvn]], [[2wzh|2wzh]], [[2w67|2w67]], [[2wca|2wca]], [[2vvs|2vvs]], [[2j4g|2j4g]], [[2w4x|2w4x]], [[2cho|2cho]], [[2xj7|2xj7]], [[2jiw|2jiw]], [[2chn|2chn]], [[2j47|2j47]], [[2wzi|2wzi]], [[2x0h|2x0h]], [[2w66|2w66]], [[2xm2|2xm2]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LTM:N-ACETYL+GLUCONOLACTAM'>LTM</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </span></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=2xm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xm1 OCA], [https://pdbe.org/2xm1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xm1 RCSB], [https://www.ebi.ac.uk/pdbsum/2xm1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xm1 ProSAT]</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=2xm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xm1 OCA], [http://pdbe.org/2xm1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xm1 RCSB], [http://www.ebi.ac.uk/pdbsum/2xm1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xm1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OGA_BACTN OGA_BACTN]] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 22: |
| | ==See Also== | | ==See Also== |
| | *[[Beta-Hexosaminidase|Beta-Hexosaminidase]] | | *[[Beta-Hexosaminidase|Beta-Hexosaminidase]] |
| | + | *[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]] |
| | + | *[[O-GlcNAcase|O-GlcNAcase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bactn]] | + | [[Category: Bacteroides thetaiotaomicron VPI-5482]] |
| - | [[Category: Beta-N-acetylhexosaminidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Davies, G J]] | + | [[Category: Davies GJ]] |
| - | [[Category: He, Y]] | + | [[Category: He Y]] |
| - | [[Category: Glycosidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
Function
OGA_BACTN Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins.
Publication Abstract from PubMed
The dynamic, intracellular, O-GlcNAc modification is of continuing interest and one whose study through targeted "chemical genetics" approaches is set to increase. Of particular importance is the inhibition of the O-GlcNAc hydrolase, O-GlcNAcase (OGA), since this provides a route to elevate cellular O-GlcNAc levels, and subsequent phenotypic evaluation. Such a small molecule approach complements other methods and potentially avoids changes in protein-protein interactions that manifest themselves in molecular biological approaches to O-GlcNAc transferase knockout or over-expression. Here we describe the kinetic, thermodynamic and three-dimensional structural analysis of a bacterial OGA analogue from Bacteroides thetaiotaomicron, BtGH84, in complex with a lactone oxime (LOGNAc) and a lactam form of N-acetylglucosamine and compare their binding signatures with that of the more potent inhibitor O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc). We show that both LOGNAc and the N-acetyl gluconolactam are significantly poorer inhibitors than PUGNAc, which may reflect poorer mimicry of transition state geometry and steric clashes with the enzyme upon binding; drawbacks that the phenyl carbamate adornment of PUGNAc helps mitigate. Implications for the design of future generations of inhibitors are discussed.
Inhibition of a bacterial O-GlcNAcase homologue by lactone and lactam derivatives: structural, kinetic and thermodynamic analyses.,He Y, Bubb AK, Stubbs KA, Gloster TM, Davies GJ Amino Acids. 2011 Mar;40(3):829-39. Epub 2010 Aug 6. PMID:20689974[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ He Y, Bubb AK, Stubbs KA, Gloster TM, Davies GJ. Inhibition of a bacterial O-GlcNAcase homologue by lactone and lactam derivatives: structural, kinetic and thermodynamic analyses. Amino Acids. 2011 Mar;40(3):829-39. Epub 2010 Aug 6. PMID:20689974 doi:10.1007/s00726-010-0700-6
|
