Haem Proteins

Abstract

Haem is used by a wide variety of proteins to carry out dozens of functions and catalyse numerous reactions. The polypeptide chains encasing the haem functional group control the accessibility, reactivity and reduction potential of the haem and, in doing so, alter the chemistry of the haem prosthetic group.

Keywords: protein structure; X‐ray crystallography; metalloproteins; dynamics

Figure 1.

Representative structures of haem‐containing proteins. Cartoon representations of several haem proteins showing the location of the haem in the protein. Shown from left to right. Top row: cytochrome b562 (four‐helix bundle), myoglobin (globin fold), nitrophorin (beta barrel). Middle row: cytochrome c, cytochrome f, bovine catalase. Bottom row, nitrite reductase (nine‐haem form). (Figure prepared using Pymol.)

Figure 2.

Close‐up views of the haem environment. (a) Space‐filling representation of the haem environment of cytochrome c. Only the edge of the haem ring (in grey) is visible, the rest of the haem is enveloped by the protein, including the propionic acid groups that point into the centre of the protein). The orange atom at the front of the pocket is the sulfur of Cys14 which is covalently bound to the haem ring. (b) Space‐filling representation of the haem environment in cytochrome P450 showing that most of the distal surface of the haem (grey) is solvent‐exposed. Water molecules occupying the distal pocket have been removed. The iron (orange) in the centre of the haem is solvent‐exposed. (c) The surroundings of the propionic acid substituents of yeast isozyme‐1‐cytochrome c. The carboxylate substituent of pyrrole ring D is completely buried in the protein and forms an ion pair with Arg38. The other carboxylate is positioned closer to the surface, but is still completely surrounded by protein residues and is not solvated. (Figure prepared using Molscript.)

Figure 3.

Structure of an electron‐transfer complex. (Left) Yeast cytochrome bc1 complex and its electron‐transfer partner cytochrome c. The large assembly is the normally membrane bound yeast cytochrome bc1 complex, the small red protein on the bottom in the box is cytochrome c. The green and red domains at the extreme bottom left and bottom right are antibody fragments needed for crystallization. (Right) An enlargement of the boxed area showing the end‐on close approach (4.5 Å) between the vinyl substituents of the haems in cytochrome c and the cytochrome c1 of the cytochrome bc1 complex. (Figure prepared using Molscript.)

Figure 4.

Substrate entrance and exit paths in haem proteins. (Top left) The conformation of P450BM‐3 (open) in the absence of substrate. (Bottom left) The same protein closed around the substrate, palmityloleic acid. The green helicies on the left side of the figure undergo the largest movements, moving towards the blue β‐sheet region on the right. (Right) The myoglobin structure showing cavities (grey spheres) thought to be occupied by substrates as they diffuse through the protein. After subjecting myoglobin crystals to xenon gas at liquid nitrogen temperatures, subsequent structure determinations have found xenon trapped in these sites. (Figure prepared using Pymol and Molscript.)

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References

Lange C and Hunte C (2002) Crystal structure of the yeast cytochrome bc1 complex with its bound substrate cytochrome c. Proceedings of the National Academy of Sciences of the USA 99: 2800–2805.

Li H and Poulos TL (1997) The structure of the cytochrome P450BM‐3 heme domain complexed with the fatty acid substrate palmitoleic acid. Nature Structural Biology 4: 140–146.

Louie GV and Brayer GD (1990) High‐resolution refinement of yeast iso‐1‐cytochrome c and comparisons with other eukaryotic cytochromes c. Journal of Molecular Biology 214: 527–555.

Pellicena P, Karow DS, Boon EM, Marletta MA and Kuriyan J (2004) Crystal structure of an oxygen‐binding heme domain related to soluble guanylate cyclases. Proceedings of the National Academy of Sciences of the USA 101: 12854–12859.

Rivera M and Zeng Y (2005) Heme oxygenase, steering dioxygen activation toward heme hydroxylation. Journal of Inorganic Biochemistry 99: 337–354.

Schotte F, Lim M, Jackson TA et al. (2003) Watching a protein as it functions with 150‐ps time‐resolve X‐ray crystallography. Science 300: 1944–1947. Also, http://www.sciencemag.org/content/vol300/issue5627/images/data/1944/DC1/1078797S2.mov

Shelnutt JA, Song X‐Z, Ma J‐G et al. (1998) Non‐planar porphyrins and their significance in proteins. Chemical Society Reviews 27: 31–41.

Vojtechovsky J, Chu K, Berendzen J, Sweet RM and Schlichting I (1999) Crystal structures of myoglobin–ligand complexes at near‐atomic resolution. Biophysical Journal 77: 2153–2174.

Weichsel A, Andersen JF, Roberts SA and Montfort WR (2000) Reversible nitric oxide binding to nitrophorin 4 from Rhodnius prolixus involves complete distal pocket burial. Nature Structural Biology 7: 551–554.

Further Reading

Dickerson RE (2005) Present at the Flood. How Structural Molecular Biology Came About. Sunderland, MA, USA: Sinauer Associates.

Branden C and Tooze J (1999) Introduction to Protein Structure. New York: Garland.

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How to Cite close
Roberts, Sue A, and Montfort, William R(Jan 2007) Haem Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003054]