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[[Image:2inx.jpg|left|200px]]
{{Seed}}
[[Image:2inx.png|left|200px]]


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{{STRUCTURE_2inx|  PDB=2inx  |  SCENE=  }}  
{{STRUCTURE_2inx|  PDB=2inx  |  SCENE=  }}  


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




==Overview==
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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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{{ABSTRACT_PUBMED_18808119}}


==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/18808119 18808119]
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]
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]
[[Category: Pseudomonas putida]]
[[Category: Pseudomonas putida]]
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[[Category: Isomerase]]
[[Category: Isomerase]]
[[Category: Ksi]]
[[Category: Ksi]]
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