The nerve tissue hemoglobin of Cerebratulus lacteus (CerHb) is the smallest naturally occurring known hemoglobin. Stabilization of the diatomic bound, species (e.g., O(2)) is achieved through a network of hydrogen bonds based on three key residues TyrB10, GlnE7, and ThrE11. The first two residues are typically associated in hemoglobins with enhanced O(2) affinity, related to hydrogen bond stabilization of the heme-bound O(2) resulting in a decrease of the ligand dissociation rates. In contrast to the above observations, the affinity of CerHb for O(2) is only moderate, and the rate of O(2) dissociation is unexpectedly high. To gain insight on the diverse molecular mechanisms controlling ligand affinities, we have analyzed w.t. CerHb and its ThrE11-&rt;Val mutant by means of joint molecular dynamics and quantum mechanics simulation techniques, complementing recent site-directed mutagenesis experiments. Our results suggest that the observed O(2) dissociation rates can only be explained through a dynamic equilibrium between high and low affinity states of the w.t. CerHb heme distal site. (copyright) 2005 Wiley-Liss, Inc.
|Titolo:||Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity|
BOLOGNESI, MARTINO (Penultimo)
|Parole Chiave:||Computer simulation; Density functional theory; Hemoglobin; Molecular dynamics; Myoglobin; Neural hemoglobin; Quantum mechanical-molecular mechanical (QM-MM)|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||15-feb-2006|
|Digital Object Identifier (DOI):||10.1002/prot.20822|
|Appare nelle tipologie:||01 - Articolo su periodico|