Crystal Structure of Cytochrome P450 (CYP105P2) from Streptomyces Peucetius and Its Conformational Changes in Response to Substrate Binding

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 May 28

PMID 27231902

Citations 6

Authors

Chang Woo Lee

Joo-Ho Lee

Hemraj Rimal

Hyun Park

Jun Hyuck Lee

Tae-Jin Oh

Affiliations

Soon will be listed here.

Abstract

Cytochrome P450 monooxygenases (CYP, EC 1.14.14.1) belong to a large family of enzymes that catalyze the hydroxylation of various substrates. Here, we present the crystal structure of CYP105P2 isolated from Streptomyces peucetius ATCC27952 at a 2.1 Å resolution. The structure shows the presence of a pseudo-ligand molecule in the active site, which was co-purified fortuitously and is presumed to be a biphenyl derivative. Comparison with previously determined substrate-bound CYP structures showed that binding of the ligand produces large and distinctive conformational changes in α2-α3, α7-α9, and the C-terminal loop regions. This structural flexibility confirms our previous observation that CYP105P2 can accommodate a broad range of ligands. The structure complexed with a pseudo-ligand provides the first molecular view of CYP105P2-ligand interactions, and it indicates the involvement of hydrophobic residues (Pro82, Ala181, Met187, Leu189, Leu193, and Ile236) in the interactions between hydrophobic ligands and CYP105P2. These results provide useful insights into the structural changes involved in the recognition of different ligands by CYP105P2.

Citing Articles

Unraveling the Role of Cytochrome P450 as a Key Regulator Lantipeptide Production in Streptomyces globisporus.

Kim D, Lee S, Kwak Y Plant Pathol J. 2023; 39(6):566-574.

PMID: 38081316 PMC: 10721394. DOI: 10.5423/PPJ.OA.08.2023.0119.

Crystal Structure and Biochemical Analysis of a Cytochrome P450 CYP101D5 from .

Subedi P, Do H, Lee J, Oh T Int J Mol Sci. 2022; 23(21).

PMID: 36362105 PMC: 9655578. DOI: 10.3390/ijms232113317.

The Cytochrome P450 OxyA from the Kistamicin Biosynthesis Cyclization Cascade is Highly Sensitive to Oxidative Damage.

Greule A, Izore T, Machell D, Hansen M, Schoppet M, De Voss J Front Chem. 2022; 10:868240.

PMID: 35464232 PMC: 9023744. DOI: 10.3389/fchem.2022.868240.

Reviewing a plethora of oxidative-type reactions catalyzed by whole cells of species.

Salama S, Habib M, Hatti-Kaul R, Gaber Y RSC Adv. 2022; 12(12):6974-7001.

PMID: 35424663 PMC: 8982256. DOI: 10.1039/d1ra08816e.

Cytochrome P450 Enzymes and Their Roles in the Biosynthesis of Macrolide Therapeutic Agents.

Cho M, Han S, Lim Y, Kim V, Kim H, Kim D Biomol Ther (Seoul). 2018; 27(2):127-133.

PMID: 30562877 PMC: 6430224. DOI: 10.4062/biomolther.2018.183.

References

Lamb D, Skaug T, Song H, Jackson C, Podust L, Waterman M . The cytochrome P450 complement (CYPome) of Streptomyces coelicolor A3(2). J Biol Chem. 2002; 277(27):24000-5. DOI: 10.1074/jbc.M111109200. View

Bentley S, Chater K, Challis G, Thomson N, James K, Harris D . Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature. 2002; 417(6885):141-7. DOI: 10.1038/417141a. View

Guengerich F . Cytochrome P450 enzymes in the generation of commercial products. Nat Rev Drug Discov. 2002; 1(5):359-66. DOI: 10.1038/nrd792. View

Ikeda H, Ishikawa J, Hanamoto A, Shinose M, Kikuchi H, Shiba T . Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis. Nat Biotechnol. 2003; 21(5):526-31. DOI: 10.1038/nbt820. View

Lamb D, Ikeda H, Nelson D, Ishikawa J, Skaug T, Jackson C . Cytochrome p450 complement (CYPome) of the avermectin-producer Streptomyces avermitilis and comparison to that of Streptomyces coelicolor A3(2). Biochem Biophys Res Commun. 2003; 307(3):610-9. DOI: 10.1016/s0006-291x(03)01231-2. View

Murshudov G, Vagin A, Dodson E . Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr. 1997; 53(Pt 3):240-55. DOI: 10.1107/S0907444996012255. View

Emsley P, Cowtan K . Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2126-32. DOI: 10.1107/S0907444904019158. View

McLean K, Clift D, Lewis D, Sabri M, Balding P, Sutcliffe M . The preponderance of P450s in the Mycobacterium tuberculosis genome. Trends Microbiol. 2006; 14(5):220-8. DOI: 10.1016/j.tim.2006.03.002. View

Lamb D, Guengerich F, Kelly S, Waterman M . Exploiting Streptomyces coelicolor A3(2) P450s as a model for application in drug discovery. Expert Opin Drug Metab Toxicol. 2006; 2(1):27-40. DOI: 10.1517/17425255.2.1.27. View

10.

Yasutake Y, Imoto N, Fujii Y, Fujii T, Arisawa A, Tamura T . Crystal structure of cytochrome P450 MoxA from Nonomuraea recticatena (CYP105). Biochem Biophys Res Commun. 2007; 361(4):876-82. DOI: 10.1016/j.bbrc.2007.07.062. View

11.

Lamb D, Waterman M, Kelly S, Guengerich F . Cytochromes P450 and drug discovery. Curr Opin Biotechnol. 2007; 18(6):504-12. DOI: 10.1016/j.copbio.2007.09.010. View

12.

Sugimoto H, Shinkyo R, Hayashi K, Yoneda S, Yamada M, Kamakura M . Crystal structure of CYP105A1 (P450SU-1) in complex with 1alpha,25-dihydroxyvitamin D3. Biochemistry. 2008; 47(13):4017-27. DOI: 10.1021/bi7023767. View

13.

Sasaki M, Tsuchido T, Matsumura Y . Molecular cloning and characterization of cytochrome P450 and ferredoxin genes involved in bisphenol A degradation in Sphingomonas bisphenolicum strain AO1. J Appl Microbiol. 2008; 105(4):1158-69. DOI: 10.1111/j.1365-2672.2008.03843.x. View

14.

Hayashi K, Sugimoto H, Shinkyo R, Yamada M, Ikeda S, Ikushiro S . Structure-based design of a highly active vitamin D hydroxylase from Streptomyces griseolus CYP105A1. Biochemistry. 2008; 47(46):11964-72. DOI: 10.1021/bi801222d. View

15.

Xu L, Fushinobu S, Ikeda H, Wakagi T, Shoun H . Crystal structures of cytochrome P450 105P1 from Streptomyces avermitilis: conformational flexibility and histidine ligation state. J Bacteriol. 2008; 191(4):1211-9. PMC: 2631996. DOI: 10.1128/JB.01276-08. View

16.

Omura T . Structural diversity of cytochrome P450 enzyme system. J Biochem. 2010; 147(3):297-306. DOI: 10.1093/jb/mvq001. View

17.

Xu L, Fushinobu S, Takamatsu S, Wakagi T, Ikeda H, Shoun H . Regio- and stereospecificity of filipin hydroxylation sites revealed by crystal structures of cytochrome P450 105P1 and 105D6 from Streptomyces avermitilis. J Biol Chem. 2010; 285(22):16844-53. PMC: 2878054. DOI: 10.1074/jbc.M109.092460. View

18.

Kanth B, Liou K, Sohng J . Homology modeling, binding site identification and docking in flavone hydroxylase CYP105P2 in Streptomyces peucetius ATCC 27952. Comput Biol Chem. 2010; 34(4):226-31. DOI: 10.1016/j.compbiolchem.2010.08.002. View

19.

Takamatsu S, Xu L, Fushinobu S, Shoun H, Komatsu M, Cane D . Pentalenic acid is a shunt metabolite in the biosynthesis of the pentalenolactone family of metabolites: hydroxylation of 1-deoxypentalenic acid mediated by CYP105D7 (SAV_7469) of Streptomyces avermitilis. J Antibiot (Tokyo). 2010; 64(1):65-71. PMC: 3030646. DOI: 10.1038/ja.2010.135. View

20.

Winn M, Ballard C, Cowtan K, Dodson E, Emsley P, Evans P . Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):235-42. PMC: 3069738. DOI: 10.1107/S0907444910045749. View