Crystal structure and properties of CYP231A2 from the thermoacidophilic archaeon Picrophilus torridus

Biochemistry
Winny W HoT L Poulos

Abstract

The crystal structure of a cytochrome P450 from the thermoacidophile Picrophilus torridus, CYP231A2 (PTO1399), has been solved. This structure reveals a wide open substrate access channel. To better understand ligand-induced structural transitions in CYP231A2, protein-ligand interactions were investigated using 4-phenylimidazole. Comparison of the ligand-free and -bound CYP231A2 structures shows conformational changes where the F and G helices swing as a single rigid body about a pivot point at the N-terminal end of the F helix, allowing the F helix region to dip toward the heme, resulting in closer contacts with the ligand. Thermal melting data illustrate that the melting temperature for CYP231A2 increases nearly 10 degrees C upon ligand binding, thus illustrating that the closed conformation is substantially more stable. Furthermore, spectroscopic data indicate that the active site is stable at pH 4.5, although, unusually, the thiolate ligand to the iron can be reversibly protonated. CYP231A2 does not exhibit structural features normally associated with thermophilic proteins such as an increase in salt bridge networks or extensive aromatic clustering. The increase in thermal stability instead is best correlated with the small...Continue Reading

References

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Jul 5, 2005·Journal of Bacteriology·Lanming ChenRoger A Garrett
Dec 14, 2006·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoy

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Citations

Sep 23, 2009·Chemical Reviews·Paul R Ortiz de Montellano
May 8, 2010·Antioxidants & Redox Signaling·Thomas C PochapskyMarina Dang
Jan 14, 2010·Journal of Biochemistry·Tsuneo Omura
Oct 19, 2010·BMC Structural Biology·Demet SirimJürgen Pleiss
Jan 5, 2011·Archaea : an International Microbiological Journal·Sonja StorbeckGunhild Layer
Feb 9, 2010·International Journal of Biological Macromolecules·Rabindra Kumar Behera, Shyamalava Mazumdar
Jan 24, 2012·Archives of Biochemistry and Biophysics·Eugene G Hrycay, Stelvio M Bandiera
Mar 12, 2020·The Journal of Biological Chemistry·Aaron G BartEmily E Scott
Mar 2, 2011·Metallomics : Integrated Biometal Science·Hirotoshi MatsumuraHiroyuki Ohno
Oct 10, 2018·Proceedings of the National Academy of Sciences of the United States of America·Zhuo LiuNitin Jain
Feb 1, 2021·The Journal of Biological Chemistry·Aaron G BartEmily E Scott
Jun 7, 2021·The FEBS Journal·Philip HartzRita Bernhardt

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