5fwg

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[[Image:5fwg.gif|left|200px]]<br /><applet load="5fwg" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="5fwg, resolution 2.0&Aring;" />
 
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'''TETRA-(5-FLUOROTRYPTOPHANYL)-GLUTATHIONE TRANSFERASE'''<br />
 
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==Overview==
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==TETRA-(5-FLUOROTRYPTOPHANYL)-GLUTATHIONE TRANSFERASE==
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The three-dimensional structures of isoenzyme 3-3 of glutathione (GSH), transferase complexed with (9R,10R)- and, (9S,10S)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene, [(9R,10R)-2 and (9S,10S)-2], which are the products of the addition of GSH, to phenanthrene 9,10-oxide, have been determined at resolutions of 1.9 and, 1.8 A, respectively. The structures indicate that the xenobiotic substrate, binding site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, and L12 from domain I (the GSH binding domain) and I111, Y115, F208, and S209 in domain II of the protein. All of these residues are located in, variable-sequence regions of the primary structure of class mu isoenzymes., Three of the eight residues (V9, I111, and S209) of isoenzyme 3-3 that are, in direct van der Waals contact with the dihydrophenanthrenyl portion of, the products are mutated (V9I, I111A, and S209A) in the related isoenzyme, 4-4. These three residues are implicated in control of the, stereoselectivity of the class mu isoenzymes. The hydroxyl group of Y115, is found to be hydrogen-bonded to the 10-hydroxyl group of (9S,10S)-2, a, fact suggesting that this residue could act as an electrophile to, stabilize the transition state for the addition of GSH to epoxides. The, Y115F mutant isoenzyme 3-3 is about 100-fold less efficient than the, native enzyme in catalyzing the addition of GSH to phenanthrene 9,10-oxide, and about 50-fold less efficient in the Michael addition of GSH to, 4-phenyl-3-buten-2-one. The side chain of Y115 is positioned so as to act, as a general-acid catalytic group for two types of reactions that would, benefit from electrophilic assistance. The results are consistent with the, notion that domain II, which harbors most of the variability in primary, structure, plays a crucial role in defining the substrate specificity of, class mu isoenzymes.
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<StructureSection load='5fwg' size='340' side='right'caption='[[5fwg]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5fwg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FWG 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]] 2&#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=FTR:FLUOROTRYPTOPHANE'>FTR</scene>, <scene name='pdbligand=GPR:(9R,10R)-9-(S-GLUTATHIONYL)-10-HYDROXY-9,10-DIHYDROPHENANTHRENE'>GPR</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=5fwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fwg OCA], [https://pdbe.org/5fwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fwg RCSB], [https://www.ebi.ac.uk/pdbsum/5fwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fwg ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GSTM1_RAT GSTM1_RAT] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. The olfactory GST may be crucial for the acuity of the olfactory process.
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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/fw/5fwg_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=5fwg ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The catalytic characteristics and structure of the M1-1 isoenzyme of rat glutathione (GSH) transferase in which all four tryptophan residues in each monomer are replaced with 5-fluorotryptophan are described. The fluorine-for-hydrogen substitution does not change the interaction of the enzyme with GSH even though two tryptophan residues (Trp7 and Trp45) are involved in direct hydrogen-bonding interactions with the substrate. The rate constants for association and dissociation of the peptide, measured by stopped-flow spectrometry, remain unchanged by the unnatural amino acid. The 5-FTrp-substituted enzyme exhibits a kcat of 73 s-1 as compared to 18 s-1 for the native enzyme toward 1-chloro-2,4-dinitrobenzene. That the increase in the turnover number is due to an enhanced rate of product release in the mutant is confirmed by the kinetics of the approach to equilibrium for binding of the product. The crystal structure of the 5-FTrp-containing enzyme was solved at a resolution of 2.0 A by difference Fourier techniques. The structure reveals local conformational changes in the structural elements that define the approach to the active site which are attributed to steric interactions of the fluorine atoms associated with 5-FTrp146 and 5-FTrp214 in domain II. These changes appear to result in the enhanced rate of product release. This structure represents the first of a protein substituted with 5-fluorotryptophan.
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==About this Structure==
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Enzymes harboring unnatural amino acids: mechanistic and structural analysis of the enhanced catalytic activity of a glutathione transferase containing 5-fluorotryptophan.,Parsons JF, Xiao G, Gilliland GL, Armstrong RN Biochemistry. 1998 May 5;37(18):6286-94. PMID:9572843<ref>PMID:9572843</ref>
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5FWG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with GPR as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] Known structural/functional Site: <scene name='pdbsite=GPS:Active Site Defined Largely By These Residues'>GPS</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=5FWG OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structure and function of the xenobiotic substrate binding site of a glutathione S-transferase as revealed by X-ray crystallographic analysis of product complexes with the diastereomers of 9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene., Ji X, Johnson WW, Sesay MA, Dickert L, Prasad SM, Ammon HL, Armstrong RN, Gilliland GL, Biochemistry. 1994 Feb 8;33(5):1043-52. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8110735 8110735]
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</div>
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[[Category: Glutathione transferase]]
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<div class="pdbe-citations 5fwg" style="background-color:#fffaf0;"></div>
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[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Armstrong, R.N.]]
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[[Category: Gilliland, G.L.]]
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[[Category: Parsons, J.F.]]
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[[Category: Xiao, G.]]
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[[Category: GPR]]
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[[Category: 5-fluorotryptophan]]
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[[Category: glutathione transferase]]
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[[Category: three-dimensional structure]]
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[[Category: unnatural amino acid]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 20:46:29 2007''
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==See Also==
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*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Rattus norvegicus]]
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[[Category: Armstrong RN]]
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[[Category: Gilliland GL]]
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[[Category: Parsons JF]]
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[[Category: Xiao G]]

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TETRA-(5-FLUOROTRYPTOPHANYL)-GLUTATHIONE TRANSFERASE

PDB ID 5fwg

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