Skip to main content
SpringerLink
Log in

Cholesterol Oxidase: Structure and Function

  • Chapter
  • First Online:
Book cover Cholesterol Binding and Cholesterol Transport Proteins:

Part of the book series: Subcellular Biochemistry ((SCBI,volume 51))

Abstract

Cholesterol oxidase is a bacterial-specific flavoenzyme that catalyzes the oxidation and isomerisation of steroids containing a 3β hydroxyl group and a double bond at the Δ5–6 of the steroid ring system. The enzyme is a member of a large family of flavin-specific oxidoreductases and is found in two different forms: one where the flavin adenine dinucleotide (FAD) cofactor is covalently linked to the protein and one where the cofactor is non-covalently bound to the protein. These two enzyme forms have been extensively studied in order to gain insight into the mechanism of flavin-mediated oxidation and the relationship between protein structure and enzyme redox potential. More recently the enzyme has been found to play an important role in bacterial pathogenesis and hence further studies are focused on its potential use for future development of novel antibacterial therapeutic agents. In this review the biochemical, structural, kinetic and mechanistic features of the enzyme are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Allain, C.C., Poon, L.S., Chan, C.S., Richmond, W., and Fu, P.C., 1974, Enzymatic determination of total serum cholesterol. Clin. Chem. 20: 470–475.

    CAS  PubMed  Google Scholar 

  • Anton, N., Santos-Aberturas, J., Mendes, M.V., Guerra, S.M., Martin, J.F., and Aparicio, J.F., 2007, PimM, a PAS domain positive regulator of pimaricin biosynthesis in Streptomyces natalensis. Microbiology 153: 3174–3183.

    Article  CAS  PubMed  Google Scholar 

  • Aparicio, J.F., Caffrey, P., Gil, J.A., and Zotchev, S.B., 2003, Polyene antibiotic biosynthesis gene clusters. Appl. Microbiol. Biotechnol. 61: 179–188.

    CAS  PubMed  Google Scholar 

  • Aparicio, J.F., Mendes, M.V., Anton, N., Recio, E., and Martin, J.F., 2004, Polyene macrolide antibiotic biosynthesis. Curr. Med. Chem. 11: 1645–1656.

    CAS  PubMed  Google Scholar 

  • Arya, S.K., Datta, M., Singh, S.P., and Malhotra, B.D., 2007, Biosensor for total cholesterol estimation using N-(2-aminoethyl)-3-aminopropyltrimethoxysilane self-assembled monolayer. Anal. Bioanal. Chem. 389: 2235–2242.

    Article  CAS  PubMed  Google Scholar 

  • Barenholz, Y., Patzer, E.J., Moore, N.F., and Wagner, R.R., 1978, Cholesterol oxidase as a probe for studying membrane composition and organization. Adv. Exp. Med. Biol. 101: 45–56.

    CAS  PubMed  Google Scholar 

  • Basu, A.K., Chattopadhyay, P., Roychoudhuri, U., and Chakraborty, R., 2007, Development of cholesterol biosensor based on immobilized cholesterol esterase and cholesterol oxidase on oxygen electrode for the determination of total cholesterol in food samples. Bioelectrochemistry 70: 375–379.

    Article  CAS  PubMed  Google Scholar 

  • Berg, O.G., Gelb, M.H., Tsai, M.D., and Jain, M.K., 2001, Interfacial enzymology: the secreted phospholipase A(2)-paradigm. Chem. Rev. 101: 2613–2654.

    Article  CAS  PubMed  Google Scholar 

  • Bittman, R., Kasireddy, C.R., Mattjus, P., and Slotte, J.P., 1994, Interaction of cholesterol with sphingomyelin in monolayers and vesicles. Biochemistry 33: 11776–11781.

    Article  CAS  PubMed  Google Scholar 

  • Brooks, C.J., and Smith, A.G., 1975, Cholesterol oxidase. Further studies of substrate specificity in relation to the analytical characterisation of steroids. J. Chromatogr. 112: 499–511.

    Article  CAS  PubMed  Google Scholar 

  • Brooks, C.J., and Smith, A.G., 1980, More on substrate specificity of cholesterol oxidase. Clin. Chem. 26: 1918.

    CAS  PubMed  Google Scholar 

  • Brunori, M., 2000, Structural dynamics of myoglobin. Biophys. Chem. 86: 221–230.

    Article  CAS  PubMed  Google Scholar 

  • Brzostek, A., Dziadek, B., Rumijowska-Galewicz, A., Pawelczyk, J., and Dziadek, J., 2007, Cholesterol oxidase is required for virulence of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 275: 1106–1112.

    Article  CAS  Google Scholar 

  • Buckland, B.C., Lilly, M.D., and Dunnill, P., 1976, The kinetics of cholesterol oxidase synthesis by Nocardia rhodocrous. Biotechnol. Bioeng. 18: 601–621.

    Article  CAS  PubMed  Google Scholar 

  • Caldinelli, L., Iametti, S., Barbiroli, A., Bonomi, F., Fessas, D., Molla, G., Pilone, M.S., and Pollegioni, L., 2005, Dissecting the structural determinants of the stability of cholesterol oxidase containing covalently bound flavin. J. Biol. Chem. 280: 22572–22581.

    Article  CAS  PubMed  Google Scholar 

  • Caldinelli, L., Iametti, S., Barbiroli, A., Fessas, D., Bonomi, F., Piubelli, L., Molla, G., and Pollegioni, L., 2008, Relevance of the flavin binding to the stability and folding of engineered cholesterol oxidase containing noncovalently bound FAD. Protein Sci. 17: 409–419.

    Article  CAS  PubMed  Google Scholar 

  • Chen, L., Lyubimov, A., Brammer, L., Vrielink, A., and Sampson, N.S., 2008, The binding and release of oxygen and hydrogen peroxide are directed by a hydrophobic tunnel in cholesterol oxidase. Biochemistry 47: 5368–5377.

    Article  CAS  PubMed  Google Scholar 

  • Cherradi, N., Defaye, G., and Chambaz, E.M., 1993, Dual subcellular localization of the 3 beta-hydroxysteroid dehydrogenase isomerase: characterization of the mitochondrial enzyme in the bovine adrenal cortex. J. Steroid Biochem. Mol. Biol. 46: 773–779.

    Article  CAS  PubMed  Google Scholar 

  • Cherradi, N., Defaye, G., and Chambaz, E.M., 1994, Characterization of the 3 beta-hydroxysteroid dehydrogenase activity associated with bovine adrenocortical mitochondria. Endocrinology 134: 1358–1364.

    Article  CAS  PubMed  Google Scholar 

  • Cherradi, N., Rossier, M.F., Vallotton, M.B., Timberg, R., Friedberg, I., Orly, J., Wang, X.J., Stocco, D.M., and Capponi, A.M., 1997, Submitochondrial distribution of three key steroidogenic proteins (steroidogenic acute regulatory protein and cytochrome p450scc and 3beta-hydroxysteroid dehydrogenase isomerase enzymes) upon stimulation by intracellular calcium in adrenal glomerulosa cells. J. Biol. Chem. 272: 7899–7907.

    Article  CAS  PubMed  Google Scholar 

  • Corbin, D.R., Grebenok, R.J., Ohnmeiss, T.E., Greenplate, J.T., and Purcell, J.P., 2001, Expression and chloroplast targeting of cholesterol oxidase in transgenic tobacco plants. Plant Physiol. 126: 1116–1128.

    Article  CAS  PubMed  Google Scholar 

  • Corbin, D.R., Greenplate, J.T., and Purcell, J.P., 1998, The identification and development of proteins for control of insects in genetically modified crops. Hort. Sci. 33: 614–617.

    CAS  Google Scholar 

  • Corbin, D.R., Greenplate, J.T., Wong, E.Y., and Purcell, J.P., 1994, Cloning of an insecticidal cholesterol oxidase gene and Its expression in bacteria and in plant protoplasts. Appl. Environ. Microbiol. 60: 4239–4244.

    CAS  PubMed  Google Scholar 

  • Coulombe, R., Yue, K.Q., Ghisla, S., and Vrielink, A., 2001, Oxygen access to the active site of cholesterol oxidase through a narrow channel is gated by an Arg-Glu pair. J. Biol. Chem. 276: 30435–30441.

    Article  CAS  PubMed  Google Scholar 

  • Deng, P., Nienhaus, K., Palladino, P., Olson, J.S., Blouin, G., Moens, L., Dewilde, S., Geuens, E., and Nienhaus, G.U., 2007, Transient ligand docking sites in Cerebratulus lacteus mini-hemoglobin. Gene 398: 208–223.

    Article  CAS  PubMed  Google Scholar 

  • El Yandouzi, E.H., and Le Grimellec, C., 1993, Effect of cholesterol oxidase treatment on physical state of renal brush border membranes: evidence for a cholesterol pool interacting weakly with membrane lipids. Biochemistry 32: 2047–2052.

    Article  PubMed  Google Scholar 

  • Eventoff, W., and Rossmann, M.G., 1975, The evolution of dehydrogenases and kinases. CRC Crit. Rev. Biochem. 3: 111–140.

    Article  CAS  PubMed  Google Scholar 

  • Fuhrmann, H., Dobeleit, G., Bellair, S., and Guck, T., 2002, Cholesterol oxidase and resistance of Rhodococcus equi to peroxidative stress in vitro in the presence of cholesterol. J. Vet. Med. B Infect. Dis. Vet. Public Health 49: 310–321.

    CAS  PubMed  Google Scholar 

  • Fukuyama, M., and Miyake, Y., 1979, Purification and some properties of cholesterol oxidase from Schizophyllum commune with covalently bound flavin. J. Biochem. (Tokyo) 85: 1183–1193.

    CAS  Google Scholar 

  • Furse, K.E., Pratt, D.A., Schneider, C., Brash, A.R., Porter, N.A., and Lybrand, T.P., 2006, Molecular dynamics simulations of arachidonic acid-derived pentadienyl radical intermediate complexes with COX-1 and COX-2: Insights into oxygenation regio- and stereoselectivity. Biochemistry 45: 3206–3218.

    Article  CAS  PubMed  Google Scholar 

  • Gadda, G., Wels, G., Pollegioni, L., Zucchelli, S., Ambrosius, D., Pilone, M.S., and Ghisla, S., 1997, Characterization of cholesterol oxidase from Streptomyces hydroscopicus and Brevibacterium sterolicum. Eur. J. Biochem. 250: 369–376.

    Article  CAS  PubMed  Google Scholar 

  • Gatfield, J., and Pieters, J., 2000, Essential role for cholesterol in entry of mycobacteria into macrophages. Science 288: 1647–1650.

    Article  CAS  PubMed  Google Scholar 

  • Gelb, M.H., Jain, M.K., Hanel, A.M., and Berg, O.G., 1995, Interfacial enzymology of glycerolipid hydrolases: lessons from secreted phospholipases A2. Ann. Rev. Biochem. 64: 653–688.

    Article  CAS  PubMed  Google Scholar 

  • Ghisla, S., and Massey, V., 1986, New flavins for old: artificial flavins as active site probes of flavoproteins. Biochem. J. 239: 1–12.

    CAS  PubMed  Google Scholar 

  • Ghisla, S., and Massey, V., 1989, Mechanism of flavoprotein-catalysed reactions. Eur. J. Biochem. 181: 1–17.

    Article  CAS  PubMed  Google Scholar 

  • Gimpl, G., and Gehrig-Burger, K., 2007, Cholesterol reporter molecules. Biosci. Rep. 27: 335–358.

    Article  CAS  PubMed  Google Scholar 

  • Greenplate, J.T., Duck, N.B., Pershing, J.C., and Purcell, J.P., 1995, Cholesterol oxidase – an oostatic and larvicidal agent active against the cotton boll weevil, Anthonomus grandis. Entomol. Exp. Appl. 74: 253–258.

    Article  CAS  Google Scholar 

  • Hofacker, I., and Schulten, K., 1998, Oxygen and proton pathways in cytochrome c oxidase. Proteins 30: 100–107.

    Article  CAS  PubMed  Google Scholar 

  • Inouye, Y., Taguchi, K., Fuki, A., Ishimaru, K., Snakamura, S., and Nomi, R., 1982, Purification and characterisation of extracellular 3beta-hydroxysteroid oxidase produced by Streptoverticillium cholesterolicum. Chem. Pharm. Bull. (Tokyo) 30: 951–958.

    CAS  Google Scholar 

  • Ishizaki, R., Hirayama, N., Shinkawa, H., Nimi, O., and Murooka, Y., 1989, Nucleotide sequence of the gene for cholesterol oxidase from a Streptomyces sp. J. Bacteriol. 171: 596–601.

    CAS  PubMed  Google Scholar 

  • Iwaki, M., Yakovlev, G., Hirst, J., Osyczka, A., Dutton, P.L., Marshall, D., and Rich, P.R., 2005, Direct observation of redox-linked histidine protonation changes in the iron-sulfur protein of the cytochrome bc(1) complex by ATR-FTIR spectroscopy. Biochemistry 44: 4230–4237.

    Article  CAS  PubMed  Google Scholar 

  • Jain, M.K., Gelb, M.H., Rogers, J., and Berg, O.G., 1995, Kinetic basis for interfacial catalysis by phospholipase A2. Meth. Enzymol. 249: 567–614.

    Article  CAS  PubMed  Google Scholar 

  • Kamei, T., Takiguchi, Y., Suzuki, H., Matsuzaki, M., and Nakamura, S., 1978, Purification of 3beta-hydroxysteroid oxidase of Streptomyces violascens origin by affinity chromatography on cholesterol. Chem. Pharm. Bull. (Tokyo) 26: 2799–2804.

    CAS  Google Scholar 

  • Kass, I.J., and Sampson, N.S., 1995, The isomerization catalyzed by Brevibacterium sterolicum cholesterol oxidase proceeds stereospecifically with one base. Biochem. Biophys. Res. Commun. 206: 688–693.

    Article  CAS  PubMed  Google Scholar 

  • Kass, I.J., and Sampson, N.S., 1998a, Evaluation of the role of His447 in the reaction catalyzed by cholesterol oxidase. Biochemistry 37: 17990–18000.

    Article  CAS  PubMed  Google Scholar 

  • Kass, I.J., and Sampson, N.S., 1998b, The importance of Glu361 position in the reaction catalyzed by cholesterol oxidase. Bioorg. Med. Chem. Lett. 8: 2663–2668.

    Article  CAS  PubMed  Google Scholar 

  • Lange, Y., 1992, Tracking cell cholesterol with cholesterol oxidase. J. Lipid Res. 33: 315–321.

    CAS  PubMed  Google Scholar 

  • Lange, Y., Matthies, H., and Steck, T.L., 1984, Cholesterol oxidase susceptibility of the red cell membrane. Biochim. Biophys. Acta 769: 551–562.

    Article  CAS  PubMed  Google Scholar 

  • Lange, Y., and Steck, T.L., 2008, Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol. Prog. Lipid Res. 47: 319–332.

    Article  CAS  PubMed  Google Scholar 

  • Lange, Y., Ye, J., and Steck, T.L., 2007, Scrambling of phospholipids activates red cell membrane cholesterol. Biochemistry 46: 2233–2238.

    Article  CAS  PubMed  Google Scholar 

  • Lario, P.I., Sampson, N., and Vrielink, A., 2003, Sub-atomic resolution crystal structure of cholesterol oxidase: what atomic resolution crystallography reveals about enzyme mechanism and the role of the FAD cofactor in redox activity. J. Mol. Biol. 326: 1635–1650.

    Article  CAS  PubMed  Google Scholar 

  • Lartillot, S., and Kedziora, P., 1990, Production, purification and some properties of cholesterol oxidase from a Streptomyces sp. Prep. Biochem. 20: 51–62.

    Article  CAS  PubMed  Google Scholar 

  • Le Lay, S., Li, Q., Proschogo, N., Rodriguez, M., Gunaratnam, K., Cartland, S., Rentero, C., Jessup, W., Mitchell, T., and Gaus, K., 2009, Caveolin-1-dependent and -independent membrane domains. J. Lipid Res. 50: 1609–1620.

    Article  PubMed  CAS  Google Scholar 

  • Li, J., Vrielink, A., Brick, P., and Blow, D.M., 1993, Crystal structure of cholesterol oxidase complexed with a steroid substrate: Implications for flavin adenine dinucleotide dependent alcohol oxidases. Biochemistry 32: 11507–11515.

    Article  CAS  PubMed  Google Scholar 

  • Lim, L., Molla, G., Guinn, N., Ghisla, S., Pollegioni, L., and Vrielink, A., 2006, Structural and kinetic analysis of the H121A mutant of cholesterol oxidase. Biochem. J. 400: 13–22.

    Article  CAS  PubMed  Google Scholar 

  • Linden, K.G., and Benisek, W.F., 1986, The amino acid sequence of a delta 5-3-oxosteroid isomerase from Pseudomonas putida biotype B. J. Biol. Chem. 261: 6454–6460.

    CAS  PubMed  Google Scholar 

  • Linder, R., 1984, Alteration of mammalian membranes by the cooperative and antagonistic actions of bacterial proteins. Biochim. Biophys. Acta 779: 432–435.

    Google Scholar 

  • Linder, R., and Bernheimer, A.W., 1982, Enzymatic oxidation of membrane cholesterol in relation to lysis of sheep erythrocytes by corynebacterial enzymes. Arch. Biochem. Biophys. 213: 395–404.

    Article  CAS  PubMed  Google Scholar 

  • Luu The, V., Lachance, Y., Labrie, C., Leblanc, G., Thomas, J.L., Strickler, R.C., and Labrie, F., 1989, Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase. Mol. Endocrinol. 3: 1310–1312.

    Article  CAS  PubMed  Google Scholar 

  • Lyubimov, A.Y., Chen, L., Sampson, N.S., and Vrielink, A., 2009, A hydrogen-bonding network is important for oxidation and isomerization in the reaction catalyzed by cholesterol oxidase. Acta Crystallogr. D 65: 1221–1231.

    Google Scholar 

  • Lyubimov, A.Y., Heard, K., Tang, H., Sampson, N.S., and Vrielink, A., 2007, Distortion of flavin geometry linked to ligand binding in cholesterol oxidase. Prot. Sci. 16: 2647–2656.

    Article  CAS  Google Scholar 

  • Lyubimov, A.Y., Lario, P.I., Moustafa, I., and Vrielink, A., 2006, Atomic resolution crystallography reveals how changes in pH shape the protein microenvironment. Nat. Chem. Biol. 2: 259–264.

    Article  CAS  PubMed  Google Scholar 

  • Martin, C.K., 1977, Microbial cleavage of sterol side chains. Adv. Appl. Microbiol. 22: 29–58.

    Article  CAS  PubMed  Google Scholar 

  • Mendes, M.V., Anton, N., Martin, J.F., and Aparicio, J.F., 2005, Characterization of the polyene macrolide P450 epoxidase from Streptomyces natalensis that converts de-epoxypimaricin into pimaricin. Biochem. J. 386: 57–62.

    Article  CAS  PubMed  Google Scholar 

  • Mendes, M.V., Recio, E., Anton, N., Guerra, S.M., Santos-Aberturas, J., Martin, J.F., and Aparicio, J.F., 2007, Cholesterol oxidases act as signaling proteins for the biosynthesis of the polyene macrolide pimaricin. Chem. Biol. 14: 279–290.

    Article  CAS  PubMed  Google Scholar 

  • Mendes, M.V., Recio, E., Fouces, R., Luiten, R., Martin, J.F., and Aparicio, J.F., 2001, Engineered biosynthesis of novel polyenes: a pimaricin derivative produced by targeted gene disruption in Streptomyces natalensis. Chem. Biol. 8: 635–644.

    Article  CAS  PubMed  Google Scholar 

  • Motteran, L., Pilone, M.S., Molla, G., Ghisla, S., and Pollegioni, L., 2001, Cholesterol oxidase from Brevibacterium sterolicum – The relationship between covalent flavinylation and redox properties. J. Biol. Chem. 276: 18024–18030.

    Article  CAS  PubMed  Google Scholar 

  • Moustafa, I., Foster, S., Lyubimov, A.Y., and Vrielink, A., 2006, Crystal structure of LAAO from Calloselasma rhodostoma with an L-phenylalanine substrate: insights into structure and mechanism. J. Mol. Biol. 364: 991–1002.

    Article  CAS  PubMed  Google Scholar 

  • Navas, J., Gonzalez-Zorn, B., Ladron, N., Garrido, P., and Vazquez-Boland, J.A., 2001, Identification and mutagenesis by allelic exchange of choE, encoding a cholesterol oxidase from the intracellular pathogen Rhodococcus equi. J. Bacteriol. 183: 4796–4805.

    Article  CAS  PubMed  Google Scholar 

  • Ohlsson, I., Nordstrom, B., and Branden, C.I., 1974, Structural and functional similarities within the coenzyme binding domains of dehydrogenases. J. Mol. Biol. 89: 339–354.

    Article  CAS  PubMed  Google Scholar 

  • Ohvo-Rekila, H., Mattjus, P., and Slotte, J.P., 1998, The influence of hydrophobic mismatch on androsterol/phosphatidylcholine interactions in model membranes. Biochim. Biophys. Acta 1372: 331–338.

    Article  CAS  PubMed  Google Scholar 

  • Pandey, A.K., and Sassetti, C.M., 2008, Mycobacterial persistence requires the utilization of host cholesterol. Proc. Natl. Acad. Sci. USA 105: 4376–4380.

    Article  CAS  PubMed  Google Scholar 

  • Piubelli, L., Pedotti, M., Molla, G., Feindler-Boeckh, S., Ghisla, S., Pilone, M.S., and Pollegioni, L., 2008, On the oxygen reactivity of flavoprotein oxidases: an oxygen access tunnel and gate in Brevibacterium sterolicum cholesterol oxidase. J. Biol. Chem. 283: 24738–24747.

    Article  CAS  PubMed  Google Scholar 

  • Pollegioni, L., Wels, G., Pilone, M.S., and Ghisla, S., 1999, Kinetic mechanisms of cholesterol oxidase from Streptomyces hygroscopicus and Brevibacterium sterolicum. Eur. J. Biochem. 263: 1–13.

    Article  Google Scholar 

  • Purcell, J.P., Greenplate, J.T., Jennings, M.G., Ryerse, J.S., Pershing, J.C., Sims, S.R., Prinsen, M.J., Corbin, D.R., Tran, M., Sammons, R.D., and Stonard, R.J., 1993, Cholesterol oxidase – a potent insecticidal protein active against boll weevil larvae. Biochem. Biophys. Res. Commun. 196: 1406–1413.

    Article  CAS  PubMed  Google Scholar 

  • Richmond, W., 1973, Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin. Chem. 19: 1350–1356.

    CAS  PubMed  Google Scholar 

  • Richmond, W., 1976, Use of cholesterol oxidase for assay of total and free cholesterol in serum by continuous-flow analysis. Clin. Chem. 22: 1579–1588.

    CAS  PubMed  Google Scholar 

  • Saam, J., Ivanov, I., Walther, M., Holzhutter, H., and Kuhn, H., 2007, Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels. Proc. Natl. Acad. Sci. USA 104: 13319–13324.

    Article  CAS  PubMed  Google Scholar 

  • Sampson, N.S., Kass, I.J., and Ghoshroy, K.B., 1998, Assessment of the role of an Ω loop of cholesterol oxidase: A truncated loop mutant has altered substrate specificity. Biochemistry 37: 5770–5778.

    Article  CAS  PubMed  Google Scholar 

  • Sauer, L.A., Chapman, J.C., and Dauchy, R.T., 1994, Topology of 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase in adrenal cortex mitochondria and microsomes. Endocrinology 134: 751–759.

    Article  CAS  PubMed  Google Scholar 

  • Sedlaczek, L., 1988, Biotransformations of steroids. Crit. Rev. Biotechnol. 7: 187–236.

    Article  CAS  PubMed  Google Scholar 

  • Slotte, J.P., 1992a, Enzyme-catalyzed oxidation of cholesterol in mixed phospholipid monolayers reveals the stoichiometry at which free cholesterol clusters disappear. Biochemistry 31: 5472–5477.

    Article  CAS  PubMed  Google Scholar 

  • Slotte, J.P., 1992b, Substrate specificity of cholesterol oxidase from Streptomyces cinnamomeus – a monolayer study. J. Steroid Biochem. Mol. Biol. 42: 521–526.

    Article  CAS  PubMed  Google Scholar 

  • Slotte, J.P., 1995, Direct observation of the action of cholesterol oxidase in monolayers. Biochim. Biophys. Acta 1259: 180–186.

    PubMed  Google Scholar 

  • Smith, A.G., and Brooks, C.J., 1974, Application of cholesterol oxidase in the analysis of steroids. J. Chromatogr. 101: 373–378.

    Article  CAS  PubMed  Google Scholar 

  • Smith, A.G., and Brooks, C.J., 1975, Studies of the substrate specificity of cholesterol oxidase from Nocardia erythropolis in the oxidation of 3-hydroxy steroids. Biochem. Soc. Trans. 3: 675–677.

    CAS  PubMed  Google Scholar 

  • Smith, A.G., and Brooks, C.J., 1976, Cholesterol oxidases: properties and applications. J. Steroid Biochem. 7: 705–713.

    Article  CAS  PubMed  Google Scholar 

  • Smith, A.G., and Brooks, C.J., 1977, The substrate specificity and stereochemistry, reversibility and inhibition of the 3-oxo steroid delta 4-delta 5-isomerase component of cholesterol oxidase. Biochem. J. 167: 121–129.

    CAS  PubMed  Google Scholar 

  • Soulimane, T., Buse, G., Bourenkov, G.P., Bartunik, H.D., Huber, R., and Than, M.E., 2000, Structure and mechanism of the aberrant ba(3)-cytochrome c oxidase from Thermus thermophilus. EMBO J. 19: 1766–1776.

    Article  CAS  PubMed  Google Scholar 

  • Talalay, P., and Wang, V.S., 1955, Enzymic isomerization of delta5-3-ketosteroids. Biochim. Biophys. Acta 18: 300–301.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, J.L., Evans, B.W., Blanco, G., Mercer, R.W., Mason, J.I., Adler, S., Nash, W.E., Isenberg, K.E., and Strickler, R.C., 1998, Site-directed mutagenesis identifies amino acid residues associated with the dehydrogenase and isomerase activities of human type I (placental) 3beta-hydroxysteroid dehydrogenase/isomerase. J. Steroid Biochem. Mol. Biol. 66: 327–334.

    Article  CAS  PubMed  Google Scholar 

  • Uwajima, T., Yagi, H., Nakamurs, S., and Terada, O., 1973, Isolation and crystallization of extracellular 3β-hydroxysteroid oxidase of Brevibacterium sterolicum nov. sp. Agr. Biol. Chem. 37: 2345–2350.

    CAS  Google Scholar 

  • Van Der Geize, R., Yam, K., Heuser, T., Wilbrink, M.H., Hara, H., Anderton, M.C., Sim, E., Dijkhuizen, L., Davies, J.E., Mohn, W.W., and Eltis, L.D., 2007, A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into Mycobacterium tuberculosis survival in macrophages. Proc. Natl. Acad. Sci. USA 104: 1947–1952.

    Article  PubMed  CAS  Google Scholar 

  • Vazquez-Boland, J.A., Kuhn, M., Berche, P., Chakraborty, T., Dominguez-Bernal, G., Goebel, W., Gonzalez-Zorn, B., Wehland, J., and Kreft, J., 2001, Listeria pathogenesis and molecular virulence determinants. Clin. Microbiol. Rev. 14: 584–640.

    Article  CAS  PubMed  Google Scholar 

  • Vidal, J.C., Espuelas, J., and Castillo, J.R., 2004, Amperometric cholesterol biosensor based on in situ reconstituted cholesterol oxidase on an immobilized monolayer of flavin adenine dinucleotide cofactor. Anal. Biochem. 333: 88–98.

    Article  CAS  PubMed  Google Scholar 

  • Vrielink, A., and Ghisla, S., 2009, Cholesterol oxidase: Biochemistry and structural features. FEBS J. 276: 6826–6843.

    Google Scholar 

  • Vrielink, A., Lloyd, L.F., and Blow, D.M., 1991, Crystal structure of cholesterol oxidase from Brevibacterium sterolicum refined at 1.8 Å resolution. J. Mol. Biol. 219: 533–554.

    Article  CAS  PubMed  Google Scholar 

  • Weinstock, D.M., and Brown, A.E., 2002, Rhodococcus equi: an emerging pathogen. Clin. Infect. Dis. 34: 1379–1385.

    Article  PubMed  Google Scholar 

  • Wilmanska, D., Dziadek, J., Sajduda, A., Milczarek, K., Jaworski, A., and Murooka, Y., 1995, Identification of cholesterol oxidase from fast-growing Mycobacterial strains and Rhododoccus sp. J. Ferment. Bioeng. 29: 119–124.

    Article  Google Scholar 

  • Wilmanska, D., and Sedlaczek, L., 1988, The kinetics of biosynthesis and some properties of an extracellular cholesterol oxidase produced by Arthrobacter sp. IM 79. Acta Microbiol. Polon. 37: 45–51.

    CAS  Google Scholar 

  • Yamashita, M., Toyama, M., Ono, H., Fujii, I., Hirayama, N., and Murooka, Y., 1998, Separation of the two reactions, oxidation and isomerization, catalyzed by Streptomyces cholesterol oxidase. Protein Eng. 11: 1075–1081.

    Article  CAS  PubMed  Google Scholar 

  • Yin, Y., Sampson, N.S., Vrielink, A., and Lario, P.I., 2001, The presence of a hydrogen bond between asparagine 485 and the pi system of FAD modulates the redox potential in the reaction catalyzed by cholesterol oxidase. Biochemistry 40: 13779–13787.

    Article  CAS  PubMed  Google Scholar 

  • Yue, Q.K., Kass, I.J., Sampson, N.S., and Vrielink, A., 1999, Crystal structure determination of cholesterol oxidase from Streptomyces and structural characterization of key active site mutants. Biochemistry 38: 4277–4286.

    Article  CAS  PubMed  Google Scholar 

  • Zajaczkowska, E., Bartoszko-Tyczkowska, A., and Sedlaczek, L., 1988, Microbiological degradation of sterols. II. Isolation of Rhodococcus sp. IM 58 mutants with a block of the cholesterol degradation pathway. Acta Microbiol. Polon. 37: 39–44.

    CAS  Google Scholar 

  • Zajaczkowska, E., and Sedlaczek, L., 1988, Microbiolgical degradation of sterols. I. Selective induction of enzyme of the cholesterol side chain cleavage in Rhodococcus sp. IM 58. Acta Microbiol. Polon. 37.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Biomedical Biomolecular and Chemical Sciences, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia

    Alice Vrielink

Authors

Corresponding author

Correspondence to Alice Vrielink .

Editor information

Editors and Affiliations

  1. Hackwood Park 11, Hexham, Northumberland, NE46 1AX, United Kingdom

    J. Robin Harris

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Vrielink, A. (2010). Cholesterol Oxidase: Structure and Function. In: Harris, J. (eds) Cholesterol Binding and Cholesterol Transport Proteins:. Subcellular Biochemistry, vol 51. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8622-8_5

Download citation

Publish with us

Policies and ethics

Search

Navigation