Hydrogen bonding to Trp beta37 is the first step in a compound pathway for hemoglobin allostery.
Human hemoglobin is widely thought to change from the R to the T quaternary structure in a single rate process requiring tens of microseconds. Here we present kinetic evidence that the R --> T allosteric pathway in hemoglobin requires more than one step. We use magnetic circular dichroism (MCD) spectroscopy of the aromatic amino acid bands to show that formation of a tryptophan-aspartate hydrogen bond in the hinge region of the dimer-dimer interface is part of an obligatory R --> T step proceeding more than a factor of 10 faster than the kinetic step previously identified in heme-band absorption studies.
Goldbeck
Robert A
RA
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA. goldbeck@chemistry.ucsc.edu
Esquerra
Raymond M
RM
Kliger
David S
DS
D002942:Circular Dichroism; D019281:Dimerization; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D020836:Protein Structure, Quaternary; D014364:Tryptophan / Q000737:chemistry*
D006454:Hemoglobins; D014364:Tryptophan