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1jvn

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(New page: 200px<br /><applet load="1jvn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jvn, resolution 2.10&Aring;" /> '''CRYSTAL STRUCTURE OF...)
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[[Image:1jvn.gif|left|200px]]<br /><applet load="1jvn" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1jvn, resolution 2.10&Aring;" />
 
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'''CRYSTAL STRUCTURE OF IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE: A TUNNEL THROUGH A (BETA/ALPHA)8 BARREL JOINS TWO ACTIVE SITES'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE: A TUNNEL THROUGH A (BETA/ALPHA)8 BARREL JOINS TWO ACTIVE SITES==
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BACKGROUND: Imidazole glycerol phosphate synthase catalyzes a two-step, reaction of histidine biosynthesis at the bifurcation point with the, purine de novo pathway. The enzyme is a new example of intermediate, channeling by glutamine amidotransferases in which ammonia generated by, hydrolysis of glutamine is channeled to a second active site where it acts, as a nucleophile. In this case, ammonia reacts in a cyclase domain to, produce imidazole glycerol phosphate and an intermediate of purine, biosynthesis. The enzyme is also a potential target for drug and herbicide, development since the histidine pathway does not occur in mammals., RESULTS: The 2.1 A crystal structure of imidazole glycerol phosphate, synthase from yeast reveals extensive interaction of the glutaminase and, cyclase catalytic domains. At the domain interface, the glutaminase active, site points into the bottom of the (beta/alpha)(8) barrel of the cyclase, domain. An ammonia tunnel through the (beta/alpha)(8) barrel connects the, glutaminase docking site at the bottom to the cyclase active site at the, top. A conserved "gate" of four charged residues controls access to the, tunnel. CONCLUSIONS: This is the first structure in which all the, components of the ubiquitous (beta/alpha)(8) barrel fold, top, bottom, and, interior, take part in enzymatic function. Intimate contacts between the, barrel domain and the glutaminase active site appear to be poised for, crosstalk between catalytic centers in response to substrate binding at, the cyclase active site. The structure provides a number of potential, sites for inhibitor development in the active sites and in a conserved, interdomain cavity.
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<StructureSection load='1jvn' size='340' side='right'caption='[[1jvn]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1jvn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JVN FirstGlance]. <br>
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1JVN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with NI, SO4 and POP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JVN OCA].
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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]] 2.1&#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=143:S-2,3-DIHYDRO-5-GLYCIN-2-YL-ISOXAZOL-3-YL-CYSTEINE'>143</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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==Reference==
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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=1jvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jvn OCA], [https://pdbe.org/1jvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jvn RCSB], [https://www.ebi.ac.uk/pdbsum/1jvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jvn ProSAT]</span></td></tr>
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Crystal structure of imidazole glycerol phosphate synthase: a tunnel through a (beta/alpha)8 barrel joins two active sites., Chaudhuri BN, Lange SC, Myers RS, Chittur SV, Davisson VJ, Smith JL, Structure. 2001 Oct;9(10):987-97. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11591353 11591353]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HIS5_YEAST HIS5_YEAST] IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The glutamine amidotransferase domain provides the ammonia necessary to the cyclase domain to produce IGP and AICAR from PRFAR.
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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/jv/1jvn_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=1jvn ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
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[[Category: Single protein]]
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[[Category: Chaudhuri BN]]
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[[Category: Chaudhuri, B.N.]]
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[[Category: Chittur SV]]
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[[Category: Chittur, S.V.]]
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[[Category: Davisson VJ]]
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[[Category: Davisson, V.J.]]
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[[Category: Lange SC]]
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[[Category: Lange, S.C.]]
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[[Category: Myers RS]]
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[[Category: Myers, R.S.]]
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[[Category: Smith JL]]
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[[Category: Smith, J.L.]]
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[[Category: NI]]
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[[Category: POP]]
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[[Category: SO4]]
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[[Category: amidotransferase]]
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[[Category: substrate channeling]]
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[[Category: tim-barrel as a substrate tunnel]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:36:48 2007''
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Current revision

CRYSTAL STRUCTURE OF IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE: A TUNNEL THROUGH A (BETA/ALPHA)8 BARREL JOINS TWO ACTIVE SITES

PDB ID 1jvn

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