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| [[Image:1v1d.gif|left|200px]] | | {{Seed}} |
| | [[Image:1v1d.png|left|200px]] |
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| {{STRUCTURE_1v1d| PDB=1v1d | SCENE= }} | | {{STRUCTURE_1v1d| PDB=1v1d | SCENE= }} |
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| '''NUCLEOPHILIC AND GENERAL ACID CATALYSIS AT PHYSIOLOGICAL PH BY A DESIGNED MINIATURE ESTERASE'''
| | ===NUCLEOPHILIC AND GENERAL ACID CATALYSIS AT PHYSIOLOGICAL PH BY A DESIGNED MINIATURE ESTERASE=== |
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| ==Overview==
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| A 31-residue peptide (Art-Est) was designed to catalyse the hydrolysis of p-nitrophenyl esters through histidine catalysis on the solvent exposed face of the alpha-helix of bovine pancreatic polypeptide. NMR spectroscopy indicated that Art-Est adopted a stable 3-dimensional structure in solution. Art-Est was an efficient catalyst with second order rate constants of up to 0.050 M(-1) s(-1). The activity of Art-Est was a consequence of the increased nucleophilicity of His-22, which had a reduced pK(a) value of 5.5 as a consequence of its interaction with His-18 and the positively charged Arg-25 and Arg-26. Mass spectrometry and NMR spectroscopy confirmed that the Art-Est catalysed hydrolysis of p-nitrophenyl esters proceeded through an acyl-enzyme intermediate. A solvent kinetic isotope effect of 1.8 indicated that the transition state preceding the acyl intermediate was stabilised through interaction with the protonated side-chain of His-18 and indicated a reaction mechanism similar to that generally observed for natural esterases. The involvement in the reaction of two histidine residues with different pK(a) values led to a bell-shaped dependence of the reaction rate on the pH of the solution. The catalytic behaviour of Art-Est indicated that designed miniature enzymes can act in a transparent mechanism based fashion with enzyme-like behaviour through the interplay of several amino acid residues.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15280952}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15280952 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15280952}} |
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| ==About this Structure== | | ==About this Structure== |
| 1V1D is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V1D OCA]. | | 1V1D is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V1D OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Hormone]] | | [[Category: Hormone]] |
| [[Category: Pancrea]] | | [[Category: Pancrea]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:57:58 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:33:12 2008'' |
