Factor VIIa: Difference between revisions
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===="His Flip" mechanism==== | ===="His Flip" mechanism==== | ||
This mechanism argues that the protonation of the substrate leaving group by His193 is equally favorable as re-protonation of Ser344 and regeneration of substrate. In order to prevent regeneration of the substrate, His193-H+ flips placing the Nδ1 proton near the leaving group. The argument against this mechanims is the need of disruption and reformation of many hydrogen bonds which seems unlikely in the short lifetime of the transition state. Additionally the principle of loss of motion would be violated<ref>PMID:3542033 </ref><ref>PMID:11170405</ref>. | This mechanism argues that the protonation of the substrate leaving group by His193 is equally favorable as re-protonation of Ser344 and regeneration of substrate. In order to prevent regeneration of the substrate, His193-H+ flips placing the Nδ1 proton near the leaving group. The argument against this mechanims is the need of disruption and reformation of many hydrogen bonds which seems unlikely in the short lifetime of the transition state. Additionally the principle of loss of motion would be violated<ref>PMID:3542033</ref><ref>PMID:11170405</ref>. | ||
[[Image:his flip1.jpg|center]] | [[Image:his flip1.jpg|center]] | ||
====Stereochemistry of the tetrahedral intermediate==== | |||
Upon attack on an amide bond, the lone electron pairs of the oxyanion and the nitrogen of the leaving group have to be antiperiplanar to the new bond. Therefore the lone pair of the amine leaving group points away from His193-H+. For the chemistry to occur the nitrogen must undergo inversion to position the lone pair for protonation by His193-H+<ref>PMID:2514538</ref>. | |||
[[Image:stereochemistry of N.jpg|center]] | |||
==References== | ==References== | ||
<references /> | <references /> | ||