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. 2012;13(7):8025-8037.
doi: 10.3390/ijms13078025. Epub 2012 Jun 28.

High resolution crystal structures of the Cerebratulus lacteus mini-Hb in the unligated and carbomonoxy states

Francesca Germani  1 , Alessandra Pesce  2 , Andrea Venturini  2 , Luc Moens  1 , Martino Bolognesi  3 , Sylvia Dewilde  1 , Marco Nardini  3
Affiliations

High resolution crystal structures of the Cerebratulus lacteus mini-Hb in the unligated and carbomonoxy states

Francesca Germani et al. Int J Mol Sci. 2012.

Abstract

The nerve tissue mini-hemoglobin from Cerebratulus lacteus (CerHb) displays an essential globin fold hosting a protein matrix tunnel held to allow traffic of small ligands to and from the heme. CerHb heme pocket hosts the distal TyrB10/GlnE7 pair, normally linked to low rates of O(2) dissociation and ultra-high O(2) affinity. However, CerHb affinity for O(2) is similar to that of mammalian myoglobins, due to a dynamic equilibrium between high and low affinity states driven by the ability of ThrE11 to orient the TyrB10 OH group relative to the heme ligand. We present here the high resolution crystal structures of CerHb in the unligated and carbomonoxy states. Although CO binds to the heme with an orientation different from the O(2) ligand, the overall binding schemes for CO and O(2) are essentially the same, both ligands being stabilized through a network of hydrogen bonds based on TyrB10, GlnE7, and ThrE11. No dramatic protein structural changes are needed to support binding of the ligands, which can freely reach the heme distal site through the apolar tunnel. A lack of main conformational changes between the heme-unligated and -ligated states grants stability to the folded mini-Hb and is a prerequisite for fast ligand diffusion to/from the heme.

Keywords: carbon monoxide; crystal structure; heme reactivity; nerve globin; protein matrix tunnel.

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Figures

Figure 1
Figure 1
A view of the heme cavity in (a) unligated-CerHb, and (b) CerHb-CO, including distal and proximal sites, and the 2Fo-Fc electron density (blue mesh, contoured at 1σ level) calculated at the end of the refinement process. Residues lining the heme pocket are shown in ball-and-stick representation (unligated-CerHb in green and CerHb-CO in yellow, respectively). The heme is seen edge on; the distal cavity is on the right of the heme.
Figure 2
Figure 2
(a) Superimposition of unligated-CerHb (green) on CerHb-CO (yellow). All helical regions are labeled according to the globin fold topology, (b) Superimposition of CerHb-O2 (cyan) on CerHb-CO (yellow), and (c) CerHb-H2O (magenta) on CerHb-CO (yellow).
Figure 3
Figure 3
Ligand stabilization at the heme distal site of CerHb. Stereo view of the distal site region in (a) CerHb-CO (yellow) and (b) CerHb-O2 (cyan). The heme iron atom is shown in orange. Hydrogen bonds are drawn as dashed lines.
Figure 3
Figure 3
Ligand stabilization at the heme distal site of CerHb. Stereo view of the distal site region in (a) CerHb-CO (yellow) and (b) CerHb-O2 (cyan). The heme iron atom is shown in orange. Hydrogen bonds are drawn as dashed lines.
Figure 4
Figure 4
Stereo view of the structural superimposition of CerHb-CO (yellow) and unligated-CerHb (green) (a) at the distal site, and (b) at the apolar tunnel region. Relevant residues have been shown in stick representation.
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