Crystal structure of human stearoyl-coenzyme A desaturase in complex with substrate

Nature Structural and Molecular Biology

Volumn 22, Issue 7, 2015, Pages 581-585

  Wang, Hui ^a   Klein, Michael G ^a   Zou, Hua ^a   Lane, Weston ^a   Snell, Gyorgy ^a   Levin, Irena ^a   Li, Ke ^a   Sang, Bi Ching ^a  

^a Takeda San Diego Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A DESATURASE; STEAROYL COENZYME A; ACYL COENZYME A; METAL; SCD1 PROTEIN, HUMAN; STEAROYL-COENZYME A;

ALPHA HELIX; ARTICLE; BINDING SITE; CATALYSIS; CRYSTAL STRUCTURE; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM MEMBRANE; ENZYME MECHANISM; ENZYME STRUCTURE; ENZYME SUBSTRATE COMPLEX; FATTY ACID DESATURATION; HUMAN; HYDROPHOBICITY; METAL BINDING; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION; CHEMICAL STRUCTURE; CHEMISTRY; METABOLISM; PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

ACYL COENZYME A; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; HUMANS; METALS; MODELS, MOLECULAR; PROTEIN CONFORMATION; STEAROYL-COA DESATURASE;

EID: 84936846476     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.3049     Document Type: Article

References (32)

1. Zhang, Z., Dales, N.A. & Winther, M.D. Opportunities and challenges in developing stearoyl-coenzyme A desaturase-1 inhibitors as novel therapeutics for human disease. J. Med. Chem. 57, 5039-5056 (2014).
2. Enoch, H.G., Catala, A. & Strittmatter, P. Mechanism of rat liver microsomal stearyl-CoA desaturase: studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid. J. Biol. Chem. 251, 5095-5103 (1976).
3. Guy, J.E., Whittle, E., Kumaran, D., Lindqvist, Y. & Shanklin, J. The crystal structure of the ivy ?4-16:0-ACP desaturase reveals structural details of the oxidized active site and potential determinants of regioselectivity. J. Biol. Chem. 282, 19863-19871 (2007).
4. Lindqvist, Y., Huang, W., Schneider, G. & Shanklin, J. Crystal structure of delta9 stearoyl-Acyl carrier protein desaturase from castor seed and its relationship to other di-iron proteins. EMBO J. 15, 4081-4092 (1996).
5. Moche, M., Shanklin, J., Ghoshal, A. & Lindqvist, Y. Azide and acetate complexes plus two iron-depleted crystal structures of the di-iron enzyme ?9 stearoyl-Acyl carrier protein desaturase: implications for oxygen activation and catalytic intermediates. J. Biol. Chem. 278, 25072-25080 (2003).
6. Whittle, E., Cahoon, E.B., Subrahmanyam, S. & Shanklin, J. A multifunctional acyl-Acyl carrier protein desaturase from Hedera helix L. (English ivy) can synthesize 16-And 18-carbon monoene and diene products. J. Biol. Chem. 280, 28169-28176 (2005).
7. Shanklin, J., Guy, J.E., Mishra, G. & Lindqvist, Y. Desaturases: emerging models for understanding functional diversification of diiron-containing enzymes. J. Biol. Chem. 284, 18559-18563 (2009).
8. Man, W.C., Miyazaki, M., Chu, K. & Ntambi, J.M. Membrane topology of mouse stearoyl-CoA desaturase 1. J. Biol. Chem. 281, 1251-1260 (2006).
9. Stefan, N. et al. Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans. Diabetologia 51, 648-656 (2008).
10. Morgan-Lappe, S.E. et al. Identification of Ras-related nuclear protein, targeting protein for Xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen. Cancer Res. 67, 4390-4398 (2007).
11. Dobrzyn, A. & Ntambi, J.M. Stearoyl-CoA desaturase as a new drug target for obesity treatment. Obes. Rev. 6, 169-174 (2005).
12. Igal, R.A. Roles of stearoylCoA desaturase-1 in the regulation of cancer cell growth, survival and tumorigenesis. Cancers (Basel) 3, 2462-2477 (2011).
13. Attie, A.D. et al. Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J. Lipid Res. 43, 1899-1907 (2002).
14. Hulver, M.W. et al. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab. 2, 251-261 (2005).
15. Liu, G. Stearoyl-CoA desaturase inhibitors: update on patented compounds. Expert. Opin. Ther. Pat. 19, 1169-1191 (2009).
16. Powell, D.A. An overview of patented small molecule stearoyl coenzyme-A desaturase inhibitors (2009-2013). Expert. Opin. Ther. Pat. 24, 155-175 (2014).
17. Shanklin, J., Whittle, E. & Fox, B.G. Eight histidine residues are catalytically essential in a membrane-Associated iron enzyme, stearoyl-CoA desaturase, and are conserved in alkane hydroxylase and xylene monooxygenase. Biochemistry 33, 12787-12794 (1994).
18. Sazinsky, M.H. & Lippard, S.J. Correlating structure with function in bacterial multicomponent monooxygenases and related diiron proteins. Acc. Chem. Res. 39, 558-566 (2006).
19. Rather, L.J. et al. Structure and mechanism of the diiron benzoyl-coenzyme A epoxidase BoxB. J. Biol. Chem. 286, 29241-29248 (2011).
20. Nordlund, P., Sjöberg, B.M. & Eklund, H. Three-dimensional structure of the free radical protein of ribonucleotide reductase. Nature 345, 593-598 (1990).
21. Heilmann, I., Mekhedov, S., King, B., Browse, J. & Shanklin, J. Identification of the Arabidopsis palmitoyl-monogalactosyldiacylglycerol delta7-desaturase gene FAD5, and effects of plastidial retargeting of Arabidopsis desaturases on the fad5 mutant phenotype. Plant Physiol. 136, 4237-4245 (2004).
22. Matsumoto, Y. et al. Crystal structure of quinol-dependent nitric oxide reductase from Geobacillus stearothermophilus. Nat. Struct. Mol. Biol. 19, 238-245 (2012).
23. Hino, T. et al. Structural basis of biological N2O generation by bacterial nitric oxide reductase. Science 330, 1666-1670 (2010).
24. Derewenda, Z.S. Rational protein crystallization by mutational surface engineering. Structure 12, 529-535 (2004).
25. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326 (1997).
26. Wang, B.C. Resolution of phase ambiguity in macromolecular crystallography. Methods Enzymol. 115, 90-112 (1985).
27. Adams, P.D. et al. Phenix: a comprehensive python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
28. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132 (2004).
29. Chen, V.B. et al. Molprobity: all-Atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12-21 (2010).
30. Collaborative Computing Project. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760-763 (1994).
31. Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).
32. Waterhouse, A.M., Procter, J.B., Martin, D.M.A., Clamp, M. & Barton, G.J. Jalview Version 2: a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189-1191 (2009).