Amide hydrogen exchange of the central B-chain helix within the T- and R-states of insulin hexamers.
Comparative analysis of the 1H-NMR spectra of human insulin shows that in the presence of the allosteric ligand, phenol, the tertiary structure of the protein is altered as evidenced by the decreased rate of amide hydrogen-deuterium exchange. In particular, exchange of amide protons in residues of the B-chain helix (B9-B20) are significantly affected suggesting either a stabilization of this helix or a reduction in the solvent accessibility of the helix in the R-state. This paper exemplifies the exchange rates of two amides (ValB18 and TyrB16) from this helix which decrease by approximately 400-fold as a result of this ligand induced conformational transition.
Hardaway
L A
LA
Department of Pharmaceutical Sciences, University of Arizona, Tucson 85721.
Brems
D N
DN
Beals
J M
JM
MacKenzie
N E
NE
D000495:Allosteric Site; D000577:Amides / Q000378:metabolism*; D003903:Deuterium; D006801:Humans; D007328:Insulin / Q000737:chemistry*; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D019800:Phenol; D010636:Phenols / Q000494:pharmacology; D017433:Protein Structure, Secondary; D011522:Protons
D000577:Amides; D007328:Insulin; D046911:Macromolecular Substances; D010636:Phenols; D011522:Protons; D019800:Phenol; D003903:Deuterium