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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	An additional explanation of the TPI mechanism proposed by Cleeland and Kreevoy stipulates the formation of a [http://en.wikipedia.org/wiki/Low-barrier_hydrogen_bond Low-barrier hydrogen bond]<ref>PMID:8009219</ref>. 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.		An additional explanation of the TPI mechanism proposed by Cleeland and Kreevoy stipulates the formation of a [http://en.wikipedia.org/wiki/Low-barrier_hydrogen_bond Low-barrier hydrogen bond]<ref>PMID:8009219</ref>. 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\|right\|400px\| '''TPI Mechanism with LBHB between His95 and O2 of substrate''' Frey and Hegeman ''Enzymatic Reaction Mechanisms'' 2007]]		[[Image:TPImechanism.png\|thumb\|right\|400px\| '''TPI Mechanism with LBHB between His95 and O2 of substrate''' Adapted from Frey and Hegeman ''Enzymatic Reaction Mechanisms'' 2007]]