1h2w: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==Overview== | ==Overview== | ||
Prolyl oligopeptidase, a member of a new family of serine peptidases, plays an important role in memory disorders. Earlier x-ray, crystallographic investigations indicated that stabilization of the, tetrahedral transition state of the reaction involved hydrogen bond, formation between the oxyanion of the tetrahedral intermediate and the OH, group of Tyr(473). The contribution of the OH group was tested with the, Y473F variant using various substrates. The charged, succinyl-Gly-Pro-4-nitroanilide was hydrolyzed with a much lower, k(cat)/K(m) compared with the neutral, benzyloxycarbonyl-G1y-Pro-2-naphthylamide, although the binding modes of, the two substrates were similar, as shown by x-ray crystallography. This, suggested that electrostatic interactions between Arg(643) and the, succinyl ... | Prolyl oligopeptidase, a member of a new family of serine peptidases, plays an important role in memory disorders. Earlier x-ray, crystallographic investigations indicated that stabilization of the, tetrahedral transition state of the reaction involved hydrogen bond, formation between the oxyanion of the tetrahedral intermediate and the OH, group of Tyr(473). The contribution of the OH group was tested with the, Y473F variant using various substrates. The charged, succinyl-Gly-Pro-4-nitroanilide was hydrolyzed with a much lower, k(cat)/K(m) compared with the neutral, benzyloxycarbonyl-G1y-Pro-2-naphthylamide, although the binding modes of, the two substrates were similar, as shown by x-ray crystallography. This, suggested that electrostatic interactions between Arg(643) and the, succinyl group competed with the productive binding mechanism. Unlike most, enzyme reactions, catalysis by the wild-type enzyme exhibited positive, activation entropy. In contrast, the activation entropy for the Y473F, variant was negative, suggesting that the tyrosine OH group is involved in, stabilizing both the transition state and the water shell at the active, site. Importantly, Tyr(473) is also implicated in the formation of the, enzyme-substrate complex. The nonlinear Arrhenius plot suggested a greater, significance of the oxyanion binding site at physiological temperature., The results indicated that Tyr(473) was more needed at high pH, at high, temperature, and with charged substrates exhibiting "internally, competitive inhibition." | ||
==About this Structure== | ==About this Structure== | ||
1H2W is a | 1H2W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with GOL as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Prolyl_oligopeptidase Prolyl oligopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.26 3.4.21.26] Structure known Active Site: AS1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H2W OCA]. | ||
==Reference== | ==Reference== | ||
| Line 23: | Line 23: | ||
[[Category: serine protease]] | [[Category: serine protease]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:57:30 2007'' | ||
Revision as of 14:52, 5 November 2007
|
PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN
OverviewOverview
Prolyl oligopeptidase, a member of a new family of serine peptidases, plays an important role in memory disorders. Earlier x-ray, crystallographic investigations indicated that stabilization of the, tetrahedral transition state of the reaction involved hydrogen bond, formation between the oxyanion of the tetrahedral intermediate and the OH, group of Tyr(473). The contribution of the OH group was tested with the, Y473F variant using various substrates. The charged, succinyl-Gly-Pro-4-nitroanilide was hydrolyzed with a much lower, k(cat)/K(m) compared with the neutral, benzyloxycarbonyl-G1y-Pro-2-naphthylamide, although the binding modes of, the two substrates were similar, as shown by x-ray crystallography. This, suggested that electrostatic interactions between Arg(643) and the, succinyl group competed with the productive binding mechanism. Unlike most, enzyme reactions, catalysis by the wild-type enzyme exhibited positive, activation entropy. In contrast, the activation entropy for the Y473F, variant was negative, suggesting that the tyrosine OH group is involved in, stabilizing both the transition state and the water shell at the active, site. Importantly, Tyr(473) is also implicated in the formation of the, enzyme-substrate complex. The nonlinear Arrhenius plot suggested a greater, significance of the oxyanion binding site at physiological temperature., The results indicated that Tyr(473) was more needed at high pH, at high, temperature, and with charged substrates exhibiting "internally, competitive inhibition."
About this StructureAbout this Structure
1H2W is a Single protein structure of sequence from [1] with GOL as ligand. Active as Prolyl oligopeptidase, with EC number 3.4.21.26 Structure known Active Site: AS1. Full crystallographic information is available from OCA.
ReferenceReference
Electrostatic effects and binding determinants in the catalysis of prolyl oligopeptidase. Site specific mutagenesis at the oxyanion binding site., Szeltner Z, Rea D, Renner V, Fulop V, Polgar L, J Biol Chem. 2002 Nov 8;277(45):42613-22. Epub 2002 Aug 28. PMID:12202494
Page seeded by OCA on Mon Nov 5 13:57:30 2007