[fighter127]

Does aspartate 102 function as a general base catalyst as part of the catalytic triad? I thought it doesn't, but my biochemistry professor said it does and explained it as such, calling it a proton acceptor for the His57 residue. On the exam, he asked a question saying to list all the general base catalysts for the chymptrypsin peptide cleavage mechanism, and since I did not list asp 102 as an answer I was docked points. My understanding (particularly from my previous organic chemistry course), is that asp 102 functions as an ELECTROSTATIC catalyst, stabilizing the developing positive charge on the nitrogen on the imidazole ring of His57, and did not participate in any proton transfer reactions as a general base catalyst. Multiple sources I found (literature, webpages, journals/other textbooks) also confirm this. If anyone who has strong knowledge about catalytic mechanisms, particularly for serine proteases can chime in and give their thoughts/advice it would be much appreciated! I don't want to get points marked off unfairly

[Babcock_Hall]

This has been a subject of at least two controversies over the years; therefore, the question does not lend itself to a simple yes or no.  There is no evidence that the proton completely transfers to the aspartate residue.  There is considerable evidence that the hydrogen bond between aspartate and histidine is unusual.  The chemical shifts of the hydrogen atom and the Nδ1 nitrogen are both atypical.  The fractionation factor is sometimes lower than is typical, and ¹J_NH is also low.  All of these can be taken as evidence that the proton is shared between the two residues, but is mostly associated with the nitrogen of the histidine residue.  Papers by Cassidy in the Frey group argue that this is a low barrier hydrogen bond.  Papers from the Bachovchin group have argued otherwise.