2inx

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[[Image:2inx.jpg|left|200px]]
 
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==Crystal Structure of Ketosteroid Isomerase D40N from Pseudomonas putida (pKSI) with bound 2,6-difluorophenol==
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The line below this paragraph, containing "STRUCTURE_2inx", creates the "Structure Box" on the page.
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<StructureSection load='2inx' size='340' side='right'caption='[[2inx]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2inx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2INX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2INX FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.5&#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=FFP:2,6-DIFLUOROPHENOL'>FFP</scene></td></tr>
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{{STRUCTURE_2inx| PDB=2inx | SCENE= }}
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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=2inx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2inx OCA], [https://pdbe.org/2inx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2inx RCSB], [https://www.ebi.ac.uk/pdbsum/2inx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2inx ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SDIS_PSEPU SDIS_PSEPU]
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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/in/2inx_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=2inx 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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Enzymes are classically proposed to accelerate reactions by binding substrates within active-site environments that are structurally preorganized to optimize binding interactions with reaction transition states rather than ground states. This is a remarkably formidable task considering the limited 0.1-1 A scale of most substrate rearrangements. The flexibility of active-site functional groups along the coordinate of substrate rearrangement, the distance scale on which enzymes can distinguish structural rearrangement, and the energetic significance of discrimination on that scale remain open questions that are fundamental to a basic physical understanding of enzyme active sites and catalysis. We bring together 1.2-1.5 A resolution X-ray crystallography, (1)H and (19)F NMR spectroscopy, quantum mechanical calculations, and transition-state analogue binding measurements to test the distance scale on which noncovalent forces can constrain the structural relaxation or translation of side chains and ligands along a specific coordinate and the energetic consequences of such geometric constraints within the active site of bacterial ketosteroid isomerase (KSI). Our results strongly suggest that packing and binding interactions within the KSI active site can constrain local side-chain reorientation and prevent hydrogen bond shortening by 0.1 A or less. Further, this constraint has substantial energetic effects on ligand binding and stabilization of negative charge within the oxyanion hole. These results provide evidence that subtle geometric effects, indistinguishable in most X-ray crystallographic structures, can have significant energetic consequences and highlight the importance of using synergistic experimental approaches to dissect enzyme function.
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'''Crystal Structure of Ketosteroid Isomerase D40N from Pseudomonas putida (pKSI) with bound 2,6-difluorophenol'''
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Testing geometrical discrimination within an enzyme active site: constrained hydrogen bonding in the ketosteroid isomerase oxyanion hole.,Sigala PA, Kraut DA, Caaveiro JM, Pybus B, Ruben EA, Ringe D, Petsko GA, Herschlag D J Am Chem Soc. 2008 Oct 15;130(41):13696-708. Epub 2008 Sep 23. PMID:18808119<ref>PMID:18808119</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2inx" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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A longstanding proposal in enzymology is that enzymes are electrostatically and geometrically complementary to the transition states of the reactions they catalyze and that this complementarity contributes to catalysis. Experimental evaluation of this contribution, however, has been difficult. We have systematically dissected the potential contribution to catalysis from electrostatic complementarity in ketosteroid isomerase. Phenolates, analogs of the transition state and reaction intermediate, bind and accept two hydrogen bonds in an active site oxyanion hole. The binding of substituted phenolates of constant molecular shape but increasing pK(a) models the charge accumulation in the oxyanion hole during the enzymatic reaction. As charge localization increases, the NMR chemical shifts of protons involved in oxyanion hole hydrogen bonds increase by 0.50-0.76 ppm/pK(a) unit, suggesting a bond shortening of 0.02 A/pK(a) unit. Nevertheless, there is little change in binding affinity across a series of substituted phenolates (DeltaDeltaG = -0.2 kcal/mol/pK(a) unit). The small effect of increased charge localization on affinity occurs despite the shortening of the hydrogen bonds and a large favorable change in binding enthalpy (DeltaDeltaH = -2.0 kcal/mol/pK(a) unit). This shallow dependence of binding affinity suggests that electrostatic complementarity in the oxyanion hole makes at most a modest contribution to catalysis of 300-fold. We propose that geometrical complementarity between the oxyanion hole hydrogen-bond donors and the transition state oxyanion provides a significant catalytic contribution, and suggest that KSI, like other enzymes, achieves its catalytic prowess through a combination of modest contributions from several mechanisms rather than from a single dominant contribution.
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*[[Ketosteroid Isomerase|Ketosteroid Isomerase]]
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== References ==
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==About this Structure==
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<references/>
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2INX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2INX OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Large Structures]]
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Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in the ketosteroid isomerase oxyanion hole., Kraut DA, Sigala PA, Pybus B, Liu CW, Ringe D, Petsko GA, Herschlag D, PLoS Biol. 2006 Apr;4(4):e99. Epub 2006 Mar 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16602823 16602823]
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[[Category: Pseudomonas putida]]
[[Category: Pseudomonas putida]]
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[[Category: Single protein]]
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[[Category: Herschlag D]]
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[[Category: Steroid Delta-isomerase]]
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[[Category: Kraut D]]
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[[Category: Caaveiro, J M.Martinez.]]
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[[Category: Martinez Caaveiro JM]]
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[[Category: Herschlag, D.]]
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[[Category: Petsko GA]]
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[[Category: Kraut, D.]]
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[[Category: Pybus B]]
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[[Category: Petsko, G A.]]
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[[Category: Ringe D]]
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[[Category: Pybus, B.]]
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[[Category: Sigala P]]
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[[Category: Ringe, D.]]
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[[Category: Sigala, P.]]
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[[Category: Active site]]
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[[Category: Binding]]
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[[Category: Charge distribution]]
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[[Category: Enzyme]]
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[[Category: Hydrogen bond]]
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[[Category: Isomerase]]
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[[Category: Ksi]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:42:01 2008''
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Current revision

Crystal Structure of Ketosteroid Isomerase D40N from Pseudomonas putida (pKSI) with bound 2,6-difluorophenol

PDB ID 2inx

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