Homework 4

Structural basis for the root effect in haemoglobin.

Mylvaganam SE, et al. Nat Struct Biol. 1996 Mar; 3(3): 275-283. PMID: 8605630; UI: 96186250.

3DB file PDB file RasMol Script

The remarkable ability of root effect haemoglobins to pump oxygen against high O2 gradients results from extreme, acid-induced reductions in O2 affinity and cooperativity. The long-sought mechanism for the root effect, revealed by the 2 angstrom crystal structure of the ligand-bound haemoglobin from Leiostomus xanthurus at pH 7.5, unexpectedly involves modulation of the R-state. Key residues strategically assemble positive-charge clusters across the allosteric beta1 beta2-interface in the R-state. At low pH, protonation of the beta N terminus and His 147(HC3)beta within these clusters is postulated to destabilize the R-state and promote the acid-triggered, allosteric R-->T switch with concomitant O2 release. Surprisingly, a set of residues specific to root effect haemoglobins recruit additional residues, conserved among most haemoglobins, to produce the root effect.
Comments: Comment in: Nat Struct Biol 1996
X Rotation Y Rotation When Hemes meet His A.A. His Fe