Two distinct distal sites modulate oxygen affinity in minihemoglobin of Cerebratulus Lacteus

M.A. MARTI; A. CRESPO; D.E. BIKIEL; M. NARDINI; M. BOLOGNESI; D.A. ESTRIN

PROTEINS: STRUCTURE, FUNCTION AND GENETICS

Año: 2006 vol. 62 p. 641 - 648

0887-3585

The nerve tissue hemoglobin ofCerebratulus lacteus (CerHb) is the smallest naturallyoccurring known hemoglobin. Stabilization ofthe diatomic bound species (e.g., O2) is achievedthrough a network of hydrogen bonds based onthree key residues TyrB10, GlnE7, and ThrE11. Thefirst two residues are typically associated in hemoglobinswith enhanced O2 affinity, related to hydrogenbond stabilization of the heme-bound O2 resultingin a decrease of the ligand dissociation rates. Incontrast to the above observations, the affinity ofCerHb for O2 is only moderate, and the rate of O2dissociation is unexpectedly high. To gain insighton the diverse molecular mechanisms controllingligand affinities, we have analyzed w.t. CerHb andits ThrE113Val mutant by means of joint moleculardynamics and quantum mechanics simulation techniques,complementing recent site-directed mutagenesisexperiments. Our results suggest that theobserved O2 dissociation rates can only be explainedthrough a dynamic equilibrium betweenhigh and low affinity states of the w.t. CerHb heme