Charge Transfer and π to π* Transitions in the Visible Spectra of Sulfheme Met Isomeric Structures.

Since the 1863 discovery of a new green hemoglobin derivative called "sulfhemoglobin", the nature of the characteristic 618 nm absorption band has been the subject of several hypotheses. The experimental spectra are a function of the observation time and interplay between two major sulfheme isomer concentrations (a three- and five-membered ring adduct), with the latter being the dominant isomer at longer times. Thus, time-dependent density functional theory (TDDFT) was used to calculate the sulfheme excited states and visualize the highest occupied molecular orbitals (HOMOs) and lowest unoccupied MOs (LUMOs) of both isomers in order to interpret the transitions between them. These two isomers have distinguishable a1u and a2u HOMO energies. Formation of the three-membered ring SA isomeric structure decreases the energy of the HOMO a1u and a2u orbitals compared to the unmodified heme due to the electron-withdrawing, sulfur-containing, three-membered ring. Conversely, formation of the SC isomeric structure decreases the energy of the HOMO a1u and a2u orbitals due to the electron-withdrawing, sulfur-containing, five-membered ring. The calculations reveal that the absorption spectrum within the 700 nm region arises from a mixture of MOs but can be characterized as π to π* transitions, while the 600 nm region is characterized by π to dπ (d yz, d xz) transitions having components of a deoxy-like derivative.

Sulfmyoglobin Conformational Change: A Role in the Decrease of Oxy-Myoglobin Functionality.

This work is focused at understanding the interaction of H2S with Myoglobin (Mb), in particular the Sulfmyoglobin (SMb) product, whose physiological role is controversial and not well understood. The scattering curves, Guinier, Kratky, Porod and P(r) plots were analyzed for oxy-Mb and oxy-Hemoglobin I (oxyHbI) in the absence and presence of H2S, using Small and Wide Angle X-ray Scattering (SAXS/WAXS) technique. Three dimensional models were also generated from the SAXS/WAXS data. The results show that SMb formation, produced by oxyMb and H2S interaction, induces a change in the protein conformation where its envelope has a very small cleft and the protein is more flexible, less rigid and compact. Based on the direct relationship between Mb's structural conformation and its functionality, we suggest that the conformational change observed upon SMb formation plays a contribution to the protein decrease in O2 affinity and, therefore, on its functionality.

Hydrogen sulfide activation in hemeproteins: the sulfheme scenario.

Traditionally known as a toxic gas, hydrogen sulfide (H2S) is now recognized as an important biological molecule involved in numerous physiological functions. Like nitric oxide (NO) and carbon monoxide (CO), H2S is produced endogenously in tissues and cells and can modulate biological processes by acting on target proteins. For example, interaction of H2S with the oxygenated form of human hemoglobin and myoglobin produces a sulfheme protein complex that has been implicated in H2S degradation. The presence of this sulfheme derivative has also been used as a marker for endogenous H2S synthesis and metabolism. Remarkably, human catalases and peroxidases also generate this sulfheme product. In this review, we describe the structural and functional aspects of the sulfheme derivative in these proteins and postulate a generalized mechanism for sulfheme protein formation. We also evaluate the possible physiological function of this complex and highlight the issues that remain to be assessed to determine the role of sulfheme proteins in H2S metabolism, detection and physiology.

Hydrogen sulfide and hemeproteins: knowledge and mysteries.

Historically, hydrogen sulfide (H(2)S) has been regarded as a poisonous gas, with a wide spectrum of toxic effects. However, like ·NO and CO, H(2)S is now referred to as a signaling gas involved in numerous physiological processes. The list of reports highlighting the physiological effects of H(2)S is rapidly expanding and several drug candidates are now being developed. As with ·NO and CO, not a single H(2)S target responsible for all the biological effects has been found till now. Nevertheless, it has been suggested that H(2)S can bind to hemeproteins, inducing different responses that can mediate its effects. For instance, the interaction of H(2)S with cytochrome c oxidase has been associated with the activation of the ATP-sensitive potassium channels, regulating muscle relaxation. Inhibition of cytochrome c oxidase by H(2)S has also been related to inducing a hibernation-like state. Although H(2)S might induce these effects by interacting with hemeproteins, the mechanisms underlying these interactions are obscure. Therefore, in this review we discuss the current state of knowledge about the interaction of H(2)S with vertebrate and invertebrate hemeproteins and postulate a generalized mechanism. Our goal is to stimulate further research aimed at evaluating plausible mechanisms that explain H(2)S reactivity with hemeproteins.

Structural determinants for the formation of sulfhemeprotein complexes.

Several hemoglobins were explored by UV-Vis and resonance Raman spectroscopy to define sulfheme complex formation. Evaluation of these proteins upon the reaction with H(2)O(2) or O(2) in the presence of H(2)S suggest: (a) the formation of the sulfheme derivate requires a HisE7 residue in the heme distal site with an adequate orientation to form an active ternary complex; (b) that the ternary complex intermediate involves the HisE7, the peroxo or ferryl species, and the H(2)S molecule. This moiety precedes and triggers the sulfheme formation.