Factor Xa: Difference between revisions
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[[Image:His flip modified.gif|right|thumb|650px| '''His flip mechanism proposed by Bachovchin in 2001'''. <ref name="his flip" />]]As stated previously, His57 removes a proton from Ser195 and transfers it to the leaving group. It can be argued that the protonated His57 could reprotonate Ser195 and regenerate the substrate. One hypothesis is that protonated His57 flips such that N1 proton could easily protonate the leaving group. <ref> PMID: 3542033 </ref> This flipped conformation has been observed in another group of serine proteases, subtilisin, in a 50% dimethylformamide solution. <ref name="his flip"> Bachovchin, W. Contributions of NMR spectroscopy to the study of hydrogen bonds in serine protease active sites. Magnetic Resonance in Chemistry; (2001); 39(Spec. Issue); 199-213. </ref> | [[Image:His flip modified.gif|right|thumb|650px| '''His flip mechanism proposed by Bachovchin in 2001'''. <ref name="his flip" />]]As stated previously, His57 removes a proton from Ser195 and transfers it to the leaving group. It can be argued that the protonated His57 could reprotonate Ser195 and regenerate the substrate. One hypothesis is that protonated His57 flips such that N1 proton could easily protonate the leaving group. <ref> PMID: 3542033 </ref> This flipped conformation has been observed in another group of serine proteases, subtilisin, in a 50% dimethylformamide solution. <ref name="his flip"> Bachovchin, W. Contributions of NMR spectroscopy to the study of hydrogen bonds in serine protease active sites. Magnetic Resonance in Chemistry; (2001); 39(Spec. Issue); 199-213. </ref> | ||
However, there are several arguments against the His flip mechanism. Flipping of His57 would require breaking and reforming many hydrogen bonds while the short lived tetrahedral intermediate is present. Also, His57 is sterically hindered by the P2 and P1’ residues of the peptide substrates. <ref> PMID: 2271520 </ref>These observations disfavor the His flip mechanism. | However, there are several arguments against the His flip mechanism. Flipping of His57 would require breaking and reforming many hydrogen bonds while the short lived tetrahedral intermediate is present. Also, His57 is sterically hindered by the P2 and P1’ residues of the peptide substrates. <ref> PMID: 2271520 </ref>These observations disfavor the His flip mechanism. | ||
====Low Barrier Hydrogen Bonds==== | ====Low Barrier Hydrogen Bonds==== | ||
