Dear Monika,

If your protein-ligand interaction is at millimolar, you need to increase 
injection volume in order to see heat change. Also, you can do the experiment 
at low temperature such as 10 degree Celsius. You can follow this paper where I 
have crystallized weak binding ligand and complemented with ITC.
https://pubmed.ncbi.nlm.nih.gov/24957055-structure-interactions-and-evolutionary-implications-of-a-domain-swapped-lectin-dimer-from-mycobacterium-smegmatis/?from_term=Dhabaleswar+Patra&from_pos=7
Structure, Interactions and Evolutionary Implications of a Domain-Swapped 
Lectin Dimer From Mycobacterium Smegmatis - 
PubMed<https://pubmed.ncbi.nlm.nih.gov/24957055-structure-interactions-and-evolutionary-implications-of-a-domain-swapped-lectin-dimer-from-mycobacterium-smegmatis/?from_term=Dhabaleswar+Patra&from_pos=7>
Crystal structure determination of the lectin domain of MSMEG_3662 from 
Mycobacterium smegmatis and its complexes with mannose and methyl-α-mannose, 
the first effort of its kind on a mycobacterial lectin, reveals a structure 
very similar to β-prism II fold lectins from plant sources, but with extens …
pubmed.ncbi.nlm.nih.gov
Hope this help.

Regards,
Dhabaleswar Patra
Purdue University, IN


________________________________
From: CCP4 bulletin board <[email protected]> on behalf of vipul panchal 
<[email protected]>
Sent: Saturday, February 22, 2020 4:25 AM
To: [email protected] <[email protected]>
Subject: Re: [ccp4bb] Contradictory result between ITC and cocrystal structure

Hi Monika,

If the protein cocrystalize with ligand doesn't mean it interacts with protein.
You have provided insufficient information here. Does the ligand is bound to 
mutant protein with atleast 2 or 3 hydrogen bonds (how many residues are 
mutated?) ? If no that means, it is just cocrystalizing but not interacting 
with mutant protein.

Another possibility is, during cocrystalization ligand concentration is very 
high so as to force the interaction which otherwise is not possible as you 
observed with ITC. In other terms, affinity is too low to be detected by ITC.

Cheers,
Vipul

On Sat, 22 Feb, 2020, 12:01 PM monika chandravanshi, 
<[email protected]<mailto:[email protected]>> 
wrote:
Dear All,

              I have a situation, where a mutant protein does not exhibit any 
heat change upon titration with cognate ligand in the ITC experiment. However, 
it co-crystallizes with the respective cognate ligand. Also, the cocrystal 
structure reveals the conservation of the hydrogen bonding networks except for 
the mutated residues. I would like to know the possible reason for the no heat 
change in the ITC experiment.

Looking forward to hearing from you.

--
-----

With Kind Regards

Monika Chandravanshi
PhD Scholar,
Department of Biosciences and Bioengineering
Indian Institute of Technology Guwahati, Guwahati India

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