I am an enzymologist and I would like to check whether the consensus of how enzymes tell thioethers from hydrocarbons on substrates is a fact or fiction. So are any of these wrong?
- S–π interactions are the sole discriminant (in enzymes at least)
- They have the same dipole
- They are the same size
- A thioether and a hydrocarbon have the same angle
From what I can tell...
Point #1 is not really in question: even if it does not account for much, aromatic residues are often found with thiols and thioethers (1/3 of protein have a methione involved in a S–π interaction). From what I can tell of point #2, 3.55 vs. 3.58 units in electronegativity (ref. wikipedia: electronegativity) won't make a difference. From point #3, while, yes, sulfide is 360 pm and methane is 380 pm (ref. wikipedia: kinetic diameter), but the former is R-S-R, R-CH2-R, so it might be different.
I am not saying they are very different: thialysine (thioether) is a toxic analog of lysine (alkane) and norleucine (alkane) of methionine (thioether; toxic for SAM usage only) due this reason. But nature has evolved to discern similar compounds.
An example, cystathionine (pictured below) is a thioether of cysteine + homoserine or homocysteine + serine (both routes exist) and one enzyme (cystathionine beta-lyase, CβL) can bind the amine on the shorter side, deprotonate the α-carbon and eliminate the thiol (homocysteine) and release the imine (hydrolysed to pyruvate), while a different enzyme (cystathione gamma-lyase, CγL) acts on the other (cysteine and ketobutyrate). The two enzymes do not catalyse both reacts as it would be wasteful (not much just a ATP>AMP). The evolution from one to the other has not be published, but from what I can tell S–π interaction is the driving force. AFAIK, the closest literature to this on cystathionine elimination is my own paper, so I know there is no answer there.