RESUMO
The chemical properties of heme proteins largely reflect the electronic properties of their heme group. Often, the porphyrin ring of the heme exhibits significant distortions from its isolated structure, but the impact of these distortions on the chemical properties of the heme is yet uncertain. A systematic study focused on the effects of the distortion of the macrocycle on the binding affinity for oxygen is presented. The results show that out-of-plane distortions decrease the binding affinity, while in-plane distortions can increase or decrease it. Among in-plane distortions, only the breathing mode, which involves the symmetric compression-expansion of the porphyrin ring, strongly modulates the binding affinity. These findings shed light into the peculiar binding affinity of Methanosarcina acetivorans protoglobin, a protein that contains a highly distorted heme. Overall, the results highlight that in-plane distortions might be exploited by certain classes of heme proteins to modulate the ligand affinity.
Assuntos
Proteínas Arqueais/química , Heme/química , Hemeproteínas/química , Oxigênio/química , Methanosarcina/metabolismo , Porfirinas/química , Teoria QuânticaRESUMO
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-->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.