Three-dimensional structure of cyanomet-sulfmyoglobin C.

Abstract

The atomic structure of horse heart cyanomet-sulfmyoglobin C has been establied by x-ray crystalographic techniques to a resolution of 2.0 A with an R value of 0.129. The protoheme IX prosthetic group of this thermodynamically stable sulfnyoglobin derivative has been converted to a chlorin in which the pyrrole ring bearing the 4-vinyl group is saturated and possesses an exocyclic thiolene ring. This study provides the three-dimensional structure of a protein with an iron-chlorin prosthetic group. The overall conformation of the surrounding polypeptide chain of the modified protein is very similar to that of the native protein. However, the addition of the sufuratom has caused a distortion of the prosthetic group from that in the native protein to result in the repositioning of the side chains of some residues in the heme pocket.

Structural determinants for the formation of sulfhemeprotein complexes

“…Myoglobin was used as the control since the properties of the sulfmyoglobin have been described in several reports [6–9]. Figure 1A shows the UV-Vis spectra obtained upon reacting metMb, metHb, metHbI and metHbI GlnE7His with H 2 O 2 and H 2 S. Formations of the sulfmyoglobin and sulfhemoglobin derivates are clearly demonstrated by the presence of the characteristic sulfheme Q band at 618 and 620nm, respectively.…”

“…In this respect, the reaction of H 2 S with Hb and Mb, in the presence of H 2 O 2 or O 2 , results in covalent modification of the heme pyrrole ring bearing the 4-vinyl group, generating the so-called sulfmyoglobin and sulfhemoglobin derivatives [6,9]. The suggested structure has been described as a chlorin with H 2 S added only across the β-β double bond of the pyrrole “B” [7–9].…”

“…The suggested structure has been described as a chlorin with H 2 S added only across the β-β double bond of the pyrrole “B” [7–9]. These sulfheme derivatives have lower O 2 affinity, which can in principle activate the K ATP channels [5].…”

“…Increased levels of sulfhemoglobin in humans can lead to rare cases of the blood disease sulfhemoglobinemia, treatments for which remain unreliable [10–12] since the mechanism underlying sulfheme complex formation has not been elucidated. The sulfheme complex has a characteristic absorption band at 620 nm that is probably due to the distortion of heme group planarity and alterations within of neighboring side-chains relative to the native protein [7–9]. It has been suggested though, that the interaction of Hb (or Mb) with H 2 O 2 produces ferryl Compound I, (Fe IV =O Por •+ ) and ferryl Compound II (Fe IV =O Por) [13], and that H 2 S may interact with these species to produce the sulfheme derivative [7,8].…”

Hydrogen sulfide activation in hemeproteins: The sulfheme scenario

“…Therefore, it is clear that the incorporation of the sulfur atom involves disruption of the ring conjugation to that of chlorin, which reduces O 2 affinity in both sulfHb and sulfMb [18, 33, 35, 36, 48]. NMR and crystallographic studies demonstrated that in fact, conversion of Mb to sulfMb did not affect the heme cavity or the overall protein structure and that the observed changes in O 2 binding arise entirely from the local electronic changes of heme-chlorin structure [34, 47, 49]. …”