Dear Deepak Alternatively, please also consider that the higher the pKa the higher the nucleophilicity of the residue/group (higher SN2 reactivity or affinity with electrophiles, like H+, perhaps the substrate of your enzyme..?, etc) .
best Horacio 2012/2/7 Deepak Oswal <deepos...@gmail.com> > Dear colleagues, > > We have solved the crystal structure of a human enzyme. The pKa of a > catalytically critical aspartic acid has increased to 6.44. It is hydrogen > bonded (2.8 Angstroms) to a water molecule that is supposed to donate a > proton during the catalysis. Can anybody help me a) interpret the > significance of this increase in pKa of the aspartic acid from 3.8 to 6.44 > in context with the catalysis? Is this advantageous or detrimental? b) How > is pKa related to an amino acids’ ability to force a water molecule to > donate a proton? c) At pH 7.4, the aspartic acid would be de-protonated > irrespective of whether the pKa is 3.8 or 6.44; isn’t that true? d) Have > similar increase in pKa values observed for aspartic acids before? I would > be grateful if anybody could explain or comment on the above queries. > > Deepak Oswal > -- Horacio Botti PhD MD Protein Crystallography Unit Institut Pasteur of Montevideo
