Triose Phosphate Isomerase: Difference between revisions

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Gregg Snider, Stephen Everse, Eran Hodis, David Canner, Eric Martz, Michal Harel, Alexander Berchansky, Jane S. Richardson, Angel Herraez

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 [[Image:Cleland1.PNG|thumb|right|400px| '''Proposed LBHB between Histidine and Enediol Intermediate.'''  Cleland & Kreevoy ''Science'' Vol. 264  1994 pg.1887-1890 ]]
-An additional explanation of the TPI mechanism involving the formation of a [http://en.wikipedia.org/wiki/Low-barrier_hydrogen_bond Low-barrier hydrogen bond] has been proposed by Cleeland and Kreevoy<ref>PMID:8009219</ref>.  The support for this LBHB arose from the rare observation of a hydrogen bond between the carbonyl oxygen of the substrate and a ''neutral'' histidine. It was reasoned that a neutral histidine was required to match the p''K''a of the enediol, a requirement for the formation of a shorter and stronger LBHB (pKa's ~ 14). It was rationalized that this strengthened hydrogen bond and ideal geometry would effectively speed up the enolization reaction. Structural evidence for this LBHB was found in a 1.2 Å crystal structure of TIM complexed with DHAP demonstrating an extremely short hydrogen bond (2.6 Å) between His95 and O2 of DHAP <ref>PMID:12509510</ref>.  Under the mechanism stipulating a LBHB between His95 and O2 of DHAP, Glu2 165 would catalyze all proton transfers between C1 and C2, while His95 would act as an electrophilic catalyst by forming a close, stabilizing LBHB with the ''cis''-enediolate intermediate.
+An additional explanation of the TPI mechanism involving the formation of a [http://en.wikipedia.org/wiki/Low-barrier_hydrogen_bond Low-barrier hydrogen bond] has been proposed by Cleeland and Kreevoy<ref>PMID:8009219</ref>.  The support for this LBHB arose from the rare observation of a hydrogen bond between the carbonyl oxygen of the substrate and a ''neutral'' histidine. It was reasoned that a neutral histidine was required to match the p''K''a of the enediol, a requirement for the formation of a shorter and stronger LBHB (pKa's ~ 14). It was rationalized that this strengthened hydrogen bond and ideal geometry would effectively speed up the enolization reaction. Structural evidence for this LBHB was found in a 1.2 Å crystal structure of TIM complexed with DHAP demonstrating an extremely short hydrogen bond (2.6 Å) between His95 and O2 of DHAP <ref>PMID:12509510</ref>.  Under the mechanism stipulating a LBHB between His95 and O2 of DHAP, Glu165 would catalyze all proton transfers between C1 and C2, while His95 would act as an electrophilic catalyst by forming a close, stabilizing LBHB with the ''cis''-enediolate intermediate.
 [[Image:mechanism4.png|thumb|left|400px| '''TPI Mechanism with LBHB between His95 and O2 of substrate''' Frey and Hegeman ''Enzymatic Reaction Mechanisms'' 2007]]