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== | ==Structure of beta-glycosidase from Sulfolobus solfataricus in complex with D-galactohydroximo-1,5-lactam== | ||
Transition-state mimicry is increasingly important both to understand | <StructureSection load='1uwt' size='340' side='right'caption='[[1uwt]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1uwt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus Saccharolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UWT 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]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GTL:(2E,3R,4R,5R,6S)-3,4,5-TRIHYDROXY-6-(HYDROXYMETHYL)-2-PIPERIDINONE'>GTL</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=1uwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uwt OCA], [https://pdbe.org/1uwt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uwt RCSB], [https://www.ebi.ac.uk/pdbsum/1uwt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uwt ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BGAL_SACS2 BGAL_SACS2] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uw/1uwt_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1uwt ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Transition-state mimicry is increasingly important both to understand enzyme mechanism and to direct the synthesis of putative therapeutic agents. X-ray crystallography is able to provide vital information on the interactions between an enzyme and the potential inhibitor. Here we report the structures, at approximately 2 A resolution, of a family GH1 beta-glycosidase from the hyperthermophilic archaeon Sulfolobus solfataricus, in complex with both covalently (derived from 2-fluoro-glycosides) and noncovalently (hydroximolactam) bound inhibitors. The enzyme has broad specificity, accommodating both gluco- and galacto-configured substrates, and the crystallographic data demonstrate that the only difference in the way these ligands bind lies in the interactions between Gln18, Glu432, and Trp433, and the hydroxyl group at the O3 and O4 positions. Inhibition by the differently configured ligands was also shown to be extremely similar, with K(i) values of 1.04 and 1.08 microM for the gluco and galacto epimers, respectively. The noncovalently bound inhibitors have a trigonal anomeric carbon, adopt a (4)H(3) (half-chair) conformation, and an interaction is formed between O2 and the catalytic nucleophile, all of which contribute to (partial) mimicry of the oxocarbenium-ion-like transition state. The inhibition of the beta-glycosidase from S. solfataricus by hydroximolactams is discussed in light of the emerging work on family GH1 glycosidase inhibition by a spectrum of putative transition-state mimics. | |||
Structural studies of the beta-glycosidase from Sulfolobus solfataricus in complex with covalently and noncovalently bound inhibitors.,Gloster TM, Roberts S, Ducros VM, Perugino G, Rossi M, Hoos R, Moracci M, Vasella A, Davies GJ Biochemistry. 2004 May 25;43(20):6101-9. PMID:15147194<ref>PMID:15147194</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1uwt" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Galactosidase 3D structures|Galactosidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharolobus solfataricus]] | |||
[[Category: Davies GJ]] | |||
[[Category: Ducros VM-A]] | |||
[[Category: Gloster TM]] | |||
[[Category: Hoos R]] | |||
[[Category: Moracci M]] | |||
[[Category: Perugino G]] | |||
[[Category: Roberts S]] | |||
[[Category: Rossi M]] | |||
[[Category: Vasella A]] | |||
Latest revision as of 16:02, 13 December 2023
Structure of beta-glycosidase from Sulfolobus solfataricus in complex with D-galactohydroximo-1,5-lactamStructure of beta-glycosidase from Sulfolobus solfataricus in complex with D-galactohydroximo-1,5-lactam
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTransition-state mimicry is increasingly important both to understand enzyme mechanism and to direct the synthesis of putative therapeutic agents. X-ray crystallography is able to provide vital information on the interactions between an enzyme and the potential inhibitor. Here we report the structures, at approximately 2 A resolution, of a family GH1 beta-glycosidase from the hyperthermophilic archaeon Sulfolobus solfataricus, in complex with both covalently (derived from 2-fluoro-glycosides) and noncovalently (hydroximolactam) bound inhibitors. The enzyme has broad specificity, accommodating both gluco- and galacto-configured substrates, and the crystallographic data demonstrate that the only difference in the way these ligands bind lies in the interactions between Gln18, Glu432, and Trp433, and the hydroxyl group at the O3 and O4 positions. Inhibition by the differently configured ligands was also shown to be extremely similar, with K(i) values of 1.04 and 1.08 microM for the gluco and galacto epimers, respectively. The noncovalently bound inhibitors have a trigonal anomeric carbon, adopt a (4)H(3) (half-chair) conformation, and an interaction is formed between O2 and the catalytic nucleophile, all of which contribute to (partial) mimicry of the oxocarbenium-ion-like transition state. The inhibition of the beta-glycosidase from S. solfataricus by hydroximolactams is discussed in light of the emerging work on family GH1 glycosidase inhibition by a spectrum of putative transition-state mimics. Structural studies of the beta-glycosidase from Sulfolobus solfataricus in complex with covalently and noncovalently bound inhibitors.,Gloster TM, Roberts S, Ducros VM, Perugino G, Rossi M, Hoos R, Moracci M, Vasella A, Davies GJ Biochemistry. 2004 May 25;43(20):6101-9. PMID:15147194[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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