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2gyi

From Proteopedia

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[[Image:2gyi.jpg|left|200px]]<br /><applet load="2gyi" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2gyi, resolution 1.6&Aring;" />
 
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'''DESIGN, SYNTHESIS, AND CHARACTERIZATION OF A POTENT XYLOSE ISOMERASE INHIBITOR, D-THREONOHYDROXAMIC ACID, AND HIGH-RESOLUTION X-RAY CRYSTALLOGRAPHIC STRUCTURE OF THE ENZYME-INHIBITOR COMPLEX'''<br />
 
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==Overview==
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==DESIGN, SYNTHESIS, AND CHARACTERIZATION OF A POTENT XYLOSE ISOMERASE INHIBITOR, D-THREONOHYDROXAMIC ACID, AND HIGH-RESOLUTION X-RAY CRYSTALLOGRAPHIC STRUCTURE OF THE ENZYME-INHIBITOR COMPLEX==
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The binding of a potent inhibitor to the enzyme D-xylose isomerase from Streptomyces olivochromogenes was examined by kinetics and X-ray crystallography. The inhibitor D-threonohydroxamic acid (THA) was designed to mimic the putative transition state of the isomerization step catalyzed by the enzyme on the substrate xylose. THA was synthesized and found to be a slow-binding competitive inhibitor with the substrate glucose. The Ki &lt; or = 100 nM was at least one million-fold less than the KM for glucose. The X-ray crystallographic structure of xylose isomerase with THA soaked into the crystals (concentration = 1000Ki) was obtained to 1.6-A resolution and refined to an R factor of 21.6%. The free enzyme and the enzyme in the xylose isomerase-THA complex show no significant structural differences. THA binds in an analogous fashion to glucose, in a linear conformation, forming ligands with Mg-1 and Mg-2 and hydrogen bonds with His53 and Lys182. On the basis of these similarities to glucose binding and its potent inhibition, we propose that THA resembles the transition state for the enzyme-catalyzed hydride transfer reaction. The THA C2 hydroxyl forms a bridging ligand between Mg-1 and Mg-2; it must be deprotonated to do so. By analogy, we propose that, during the catalytic reaction, C2 of the substrate glucose is deprotonated, and that this proton can be moved to the C1 hydroxyl concomitant with hydride transfer. We find evidence for metal movement during catalysis upon deprotonation of the C2 hydroxyl, to allow formation of a bridging ligand.(ABSTRACT TRUNCATED AT 250 WORDS)
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<StructureSection load='2gyi' size='340' side='right'caption='[[2gyi]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2gyi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_olivochromogenes Streptomyces olivochromogenes]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1gyi 1gyi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GYI FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYA:2,3,4,N-TETRAHYDROXY-BUTYRIMIDIC+ACID'>HYA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gyi OCA], [https://pdbe.org/2gyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gyi RCSB], [https://www.ebi.ac.uk/pdbsum/2gyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gyi ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/XYLA_STROL XYLA_STROL] Involved in D-xylose catabolism.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gy/2gyi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2gyi ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2GYI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_olivochromogenes Streptomyces olivochromogenes] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=HYA:'>HYA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1GYI. Active as [http://en.wikipedia.org/wiki/Xylose_isomerase Xylose isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.5 5.3.1.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GYI OCA].
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*[[D-xylose isomerase 3D structures|D-xylose isomerase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Design, synthesis, and characterization of a potent xylose isomerase inhibitor, D-threonohydroxamic acid, and high-resolution X-ray crystallographic structure of the enzyme-inhibitor complex., Allen KN, Lavie A, Petsko GA, Ringe D, Biochemistry. 1995 Mar 21;34(11):3742-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7893671 7893671]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Streptomyces olivochromogenes]]
[[Category: Streptomyces olivochromogenes]]
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[[Category: Xylose isomerase]]
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[[Category: Allen KN]]
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[[Category: Allen, K N.]]
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[[Category: Lavie A]]
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[[Category: Lavie, A.]]
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[[Category: Petsko GA]]
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[[Category: Petsko, G A.]]
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[[Category: Ringe D]]
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[[Category: Ringe, D.]]
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[[Category: HYA]]
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[[Category: MG]]
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[[Category: isomerase(intramolecular oxidoreductase)]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:36:23 2008''
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Current revision

DESIGN, SYNTHESIS, AND CHARACTERIZATION OF A POTENT XYLOSE ISOMERASE INHIBITOR, D-THREONOHYDROXAMIC ACID, AND HIGH-RESOLUTION X-RAY CRYSTALLOGRAPHIC STRUCTURE OF THE ENZYME-INHIBITOR COMPLEX

PDB ID 2gyi

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