Hi Kevin,

Hate to point this out, but under pH 7.0, the protonation state of water is not 
50:50, and it is not a good acid.  The H30+ concentration of pure water is 
10^-7 Molar.  In pure water (assuming 55.5 M) only 1:555,000,000 water 
molecules is in the protonated, charged state (H3O+).  This is why when an 
enzyme uses water in its mechanism as a nucleophile, base, or acid, there is 
usually an acid/base catalyst or  metal that protonates or deprotonates the 
water to 'activate it'. 


Best regards,

Z


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Zachary A. Wood, Ph.D.
Assistant Professor                      
Department of Biochemistry & Molecular Biology
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Life Sciences Building, Rm A426B
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On Feb 7, 2012, at 11:22 AM, Kevin Jin wrote:

> As we know, the pKa of water is 15.7. Under pH 7.0, its protonation
> should be 50/50.
> In this case, we may need to consider water in two formats:
> 
> H2O vs. H3O+
> 
> When we say water as acid, it usually stands for H3O+ in chemistry. In
> chemical equation, H+ represents H3O+.
> 
> In enzyme catalysis, water as a general acid sounds reasonable under
> pH 7.0. In some famous paper, water has been concluded as the general
> base (pKa 15.7) to deprotonate an alpha hydrogen (pKa ~ 22) or a
> hydrogen from a sp3 hybridized carbon (pKa ~36). This logic may need
> to be reconsidered.
> .
> Recently, I have read papers for pKa perturbation. I am also
> interested in the general base of Asp and Glu in enzyme catalysis.
> 
> 
> I will be very happy to read your paper in the future.
> 
> Regards,
> 
> Kevin Jin
> 
> On Tue, Feb 7, 2012 at 3:48 AM, Deepak Oswal <[email protected]> wrote:
>> 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
> 

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