Xenohormone question

[KameZ]

I understand that some substances can mimic hormones because they are the same "shape" and they bond to the hormone receptors to create similar effects.

My question is, which part of the molecule bonds to the receptor? Is it different with all hormones and receptors? I'm trying to find out if a molecule of Substance B can fit into the receptor for Substance A, and I'm not sure how to go about doing this.

Edited May 7, 2015 by KameZ

[Elite Engineer]

It depends on the original substrate that binds to the receptor and how the competitive molecule's appearance/ properties. Could be as simple as a

 

rightly placed functional group. For example:

 

Pyridoxal phosphate binds to ornithine decarboxylase reversibly. However when difluoromethylornithine (DMFO) is bound to pyridoxal phosphate

 

the enzyme is inactivated by covalently bonding the serine residue to the DFMO molecule. This is a small modification done to the molecule, but

 

nonethless inhibits enzyme activity. The same thing happens with receptors. All it takes is a modification with a functional group or as small molecule!

 

~ee

[CharonY]

I understand that some substances can mimic hormones because they are the same "shape" and they bond to the hormone receptors to create similar effects.

My question is, which part of the molecule bonds to the receptor? Is it different with all hormones and receptors? I'm trying to find out if a molecule of Substance B can fit into the receptor for Substance A, and I'm not sure how to go about doing this.

 

The simple answer is "whatever fits". As you specified similar function (as opposed to simple steric inhibition), a simple way to imagine it is that in order for that to happen, the addition of the molecule in question should result in confirmational changes in the receptor. I.e. by binding to it, in whatever form or shape changes the thermodynamic stability of the receptor.

What part of the molecule actually "fits" depends on the receptor and what properties it has to accept a molecule and typically involves a fair number of interactions at their respective surfaces (which can be ionic, hydrogen bonds, hydrophobic interactions etc). For certain ligand classes there are binding motifs identified in receptors (i.e. the amino acids involved in these interactions). As a rule, interactions of novel ligands is incredibly hard and the pharmacological industry would shell out a lot of money for quick and easy solutions.

 

As it is, on the computational side there are ligand docking softwares that help in predicting potential interactions. But again it is not a trivial thing.