Re: Why is histidine found in the active sites of so many enzymes?

Jithesh,

Histidine is found so often in active sites of enzymes because the
imidazole ring at the end of this amino acid’s side chain can perform many
different roles in catalysis.  As you correctly suggested, the pKa of about
6 is one important factor.  This pKa means that the histidine can be either
protonated or deprotonated at physiological pH, depending on the particular
environment in the active site.  When it is protonated, histidine can act
as a general acid during catalysis, donating its proton to the substrate. 
When deprotonated, histidine can act as a general base.  One family of
enzymes, the ribonucleases, hydrolyze the phosphodiester bonds in RNA.  A
key part of their catalytic machinery in a pair of histidines, one of which
is protonated and one that is not.  The latter acts as a base, and the
former acts as an acid, in a mechanism that utilizes both acid and base
catalysis.  A nice animation of the ribonuclease mechanism can be found at: 
 http://www.kingsu.ab.ca/%7Ehank/Course%20files/Biochemistry/ribonuclease.htm

Another function of histidine is as a ligand for metal ions.  Many enzymes
use metal ions for catalysis, and contain a set of ligands that coordinate
to the metal ion in order to hold it in place in the active site.  Ligands
must be able to function as Lewis bases, which are atoms that can donate
electrons.  The nitrogen atoms of the imidazole ring of histidine make it a
good Lewis base, so it is good at coordinating to metal ions and is
frequently found in metalloenzymes.