Generally speaking, in serine proteases, the three residues of the classic catalytic triad each have a specific role in the catalysis. There are a bunch of examples showing that mutant of His to Ala abolish the activity of an enzyme. However, in some papers, a mutant of His to Ala remains a little activity (very small compered to WT). I read one of these papers and found an example: "H157A had only 5.8% of the Kcat activity..., which supposedly performed catalysis aided by a water molecule in the active cleft". I wonder if the water molecule can do that or something else happen in the pocket of this enzyme?
Histidine is a constituent of proteins . Histidine is very important in hemoglobin, the Krebs cycle, proton shuttling and maintaining an acid/base balance in the blood and tissue of animals .
His in the catalytic triade accepts a proton and thereby stabilises the transition state. A water molecule can do that too, but the pKa is different.
Hi there,
Histidine in the catalytic triad has a double role: making oxygen of serine more nucleophilic to attack the carbonyl of the peptide bond and then, in a second step, making water molecule more nucleophilic to attack carbonyl of the acyl enzyme. The water molecule is actually one of the reactants (quite normal as the reaction is hydrolysis!). Therefore the reaction is occuring even in absence of enzyme (at a very slow rate) and in the enzyme mutated for any of the triad residues.
Engelbert Buxbaum: Could you explain more about the difference of the pKa which has an impact on the role of water molecule?
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