Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Recent Advances in the Understanding of the Reaction Chemistries of the Heme Catabolizing Enzymes HO and BVR Based on High Resolution Protein Structures

Author(s): Masakazu Sugishima*, Kei Wada and Keiichi Fukuyama*

Volume 27, Issue 21, 2020

Page: [3499 - 3518] Pages: 20

DOI: 10.2174/0929867326666181217142715

open access plus


In mammals, catabolism of the heme group is indispensable for life. Heme is first cleaved by the enzyme Heme Oxygenase (HO) to the linear tetrapyrrole Biliverdin IXα (BV), and BV is then converted into bilirubin by Biliverdin Reductase (BVR). HO utilizes three Oxygen molecules (O2) and seven electrons supplied by NADPH-cytochrome P450 oxidoreductase (CPR) to open the heme ring and BVR reduces BV through the use of NAD(P)H. Structural studies of HOs, including substrate-bound, reaction intermediate-bound, and several specific inhibitor-bound forms, reveal details explaining substrate binding to HO and mechanisms underlying-specific HO reaction progression. Cryo-trapped structures and a time-resolved spectroscopic study examining photolysis of the bond between the distal ligand and heme iron demonstrate how CO, produced during the HO reaction, dissociates from the reaction site with a corresponding conformational change in HO. The complex structure containing HO and CPR provides details of how electrons are transferred to the heme-HO complex. Although the tertiary structure of BVR and its complex with NAD+ was determined more than 10 years ago, the catalytic residues and the reaction mechanism of BVR remain unknown. A recent crystallographic study examining cyanobacterial BVR in complex with NADP+ and substrate BV provided some clarification regarding these issues. Two BV molecules are bound to BVR in a stacked manner, and one BV may assist in the reductive catalysis of the other BV. In this review, recent advances illustrated by biochemical, spectroscopic, and crystallographic studies detailing the chemistry underlying the molecular mechanism of HO and BVR reactions are presented.

Keywords: X-ray crystallography, Protein structure, Redox complex, Heme metabolism, Enzymatic reaction, Ligand discrimination, Stacked substrate-binding mode.

Tenhunen, R.; Marver, H.S.; Schmid, R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. USA, 1968, 61(2), 748-755.
[] [PMID: 4386763]
Tenhunen, R.; Marver, H.S.; Schmid, R. Microsomal heme oxygenase. Characterization of the enzyme. J. Biol. Chem., 1969, 244(23), 6388-6394.
[PMID: 4390967]
Ryter, S.W.; Otterbein, L.E.; Morse, D.; Choi, A.M. Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol. Cell. Biochem., 2002, 234-235(1-2), 249-263.
[] [PMID: 12162441]
Morikawa, T.; Kajimura, M.; Nakamura, T.; Hishiki, T.; Nakanishi, T.; Yukutake, Y.; Nagahata, Y.; Ishikawa, M.; Hattori, K.; Takenouchi, T.; Takahashi, T.; Ishii, I.; Matsubara, K.; Kabe, Y.; Uchiyama, S.; Nagata, E.; Gadalla, M.M.; Snyder, S.H.; Suematsu, M. Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway. Proc. Natl. Acad. Sci. USA, 2012, 109(4), 1293-1298.
[] [PMID: 22232681]
Shintani, T.; Iwabuchi, T.; Soga, T.; Kato, Y.; Yamamoto, T.; Takano, N.; Hishiki, T.; Ueno, Y.; Ikeda, S.; Sakuragawa, T.; Ishikawa, K.; Goda, N.; Kitagawa, Y.; Kajimura, M.; Matsumoto, K.; Suematsu, M. Cystathionine beta-synthase as a carbon monoxide-sensitive regulator of bile excretion. Hepatology, 2009, 49(1), 141-150.
[] [PMID: 19085910]
Dioum, E.M.; Rutter, J.; Tuckerman, J.R.; Gonzalez, G.; Gilles-Gonzalez, M.A.; McKnight, S.L. NPAS2: a gas-responsive transcription factor. Science, 2002, 298(5602), 2385-2387.
[] [PMID: 12446832]
Terry, M.J.; Linley, P.J.; Kohchi, T. Making light of it: the role of plant haem oxygenases in phytochrome chromophore synthesis. Biochem. Soc. Trans., 2002, 30(4), 604-609.
[] [PMID: 12196146]
Pendrak, M.L.; Chao, M.P.; Yan, S.S.; Roberts, D.D. Heme oxygenase in Candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to alpha-biliverdin. J. Biol. Chem., 2004, 279(5), 3426-3433.
[] [PMID: 14615478]
Frankenberg-Dinkel, N. Bacterial heme oxygenases. Antioxid. Redox Signal., 2004, 6(5), 825-834.
[PMID: 15345142]
Kikuchi, G.; Yoshida, T. Heme catabolism by the reconstituted heme oxygenase system. Ann. Clin. Res., 1976, 8(Suppl. 17), 10-17.
[PMID: 827230]
Kikuchi, G.; Yoshida, T. Function and induction of the microsomal heme oxygenase. Mol. Cell. Biochem., 1983, 53-54(1-2), 163-183.
[] [PMID: 6353193]
Kikuchi, G.; Yoshida, T.; Noguchi, M. Heme oxygenase and heme degradation. Biochem. Biophys. Res. Commun., 2005, 338(1), 558-567.
[] [PMID: 16115609]
Huber, W.J., III; Backes, W.L. Expression and characterization of full-length human heme oxygenase-1: the presence of intact membrane-binding region leads to increased binding affinity for NADPH cytochrome P450 reductase. Biochemistry, 2007, 46(43), 12212-12219.
[] [PMID: 17915953]
Huber, W.J., III; Marohnic, C.C.; Peters, M.; Alam, J.; Reed, J.R.; Masters, B.S.; Backes, W.L. Measurement of membrane-bound human heme oxygenase-1 activity using a chemically defined assay system. Drug Metab. Dispos., 2009, 37(4), 857-864.
[] [PMID: 19131520]
Wilks, A.; Black, S.M.; Miller, W.L.; Ortiz de Montellano, P.R. Expression and characterization of truncated human heme oxygenase (hHO-1) and a fusion protein of hHO-1 with human cytochrome P450 reductase. Biochemistry, 1995, 34(13), 4421-4427.
[] [PMID: 7703255]
Wilks, A.; Ortiz de Montellano, P.R. Rat liver heme oxygenase. High level expression of a truncated soluble form and nature of the meso-hydroxylating species. J. Biol. Chem., 1993, 268(30), 22357-22362.
[PMID: 8226746]
Beale, S.I. Biosynthesis of Phycobilins. Chem. Rev., 1993, 93, 785-802.
Rockwell, N.C.; Su, Y.S.; Lagarias, J.C. Phytochrome structure and signaling mechanisms. Annu. Rev. Plant Biol., 2006, 57, 837-858.
[] [PMID: 16669784]
Frankenberg, N.; Lagarias, J.C. Biosynthesis and biological functions of bilins in: The Porphyrin Handbook; Kadish, K.M.; Smith, K.M; Guilard, R., Ed.; Academic Press: San Diego, 2003, pp. 211-235.
Kohchi, T.; Mukougawa, K.; Frankenberg, N.; Masuda, M.; Yokota, A.; Lagarias, J.C. The Arabidopsis HY2 gene encodes phytochromobilin synthase, a ferredoxin-dependent biliverdin reductase. Plant Cell, 2001, 13(2), 425-436.
[] [PMID: 11226195]
Dammeyer, T.; Frankenberg-Dinkel, N. Function and distribution of bilin biosynthesis enzymes in photosynthetic organisms. Photochem. Photobiol. Sci., 2008, 7(10), 1121-1130.
[] [PMID: 18846276]
Ikeuchi, M.; Ishizuka, T. Cyanobacteriochromes: a new superfamily of tetrapyrrole-binding photoreceptors in cyanobacteria. Photochem. Photobiol. Sci., 2008, 7(10), 1159-1167.
[] [PMID: 18846279]
Chen, Y.R.; Su, Y.S.; Tu, S.L. Distinct phytochrome actions in nonvascular plants revealed by targeted inactivation of phytobilin biosynthesis. Proc. Natl. Acad. Sci. USA, 2012, 109(21), 8310-8315.
[] [PMID: 22566621]
Singleton, J.W.; Laster, L. Biliverdin reductase of guinea pig liver. J. Biol. Chem., 1965, 240(12), 4780-4789.
[PMID: 4378982]
Baranano, D.E.; Rao, M.; Ferris, C.D.; Snyder, S.H. Biliverdin reductase: a major physiologic cytoprotectant. Proc. Natl. Acad. Sci. USA, 2002, 99(25), 16093-16098.
[] [PMID: 12456881]
Stocker, R.; Yamamoto, Y.; McDonagh, A.F.; Glazer, A.N.; Ames, B.N. Bilirubin is an antioxidant of possible physiological importance. Science, 1987, 235(4792), 1043-1046.
[] [PMID: 3029864]
McDonagh, A.F.; Palma, L.A.; Lightner, D.A. Blue light and bilirubin excretion. Science, 1980, 208(4440), 145-151.
[] [PMID: 7361112]
Lerner-Marmarosh, N.; Shen, J.; Torno, M.D.; Kravets, A.; Hu, Z.; Maines, M.D. Human biliverdin reductase: a member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity. Proc. Natl. Acad. Sci. USA, 2005, 102(20), 7109-7114.
[] [PMID: 15870194]
Kravets, A.; Hu, Z.; Miralem, T.; Torno, M.D.; Maines, M.D. Biliverdin reductase, a novel regulator for induction of activating transcription factor-2 and heme oxygenase-1. J. Biol. Chem., 2004, 279(19), 19916-19923.
[] [PMID: 14988408]
Schluchter, W.M.; Glazer, A.N. Characterization of cyanobacterial biliverdin reductase. Conversion of biliverdin to bilirubin is important for normal phycobiliprotein biosynthesis. J. Biol. Chem., 1997, 272(21), 13562-13569.
[] [PMID: 9153203]
Kikuchi, A.; Park, S.Y.; Miyatake, H.; Sun, D.; Sato, M.; Yoshida, T.; Shiro, Y. Crystal structure of rat biliverdin reductase. Nat. Struct. Biol., 2001, 8(3), 221-225.
[] [PMID: 11224565]
Whitby, F.G.; Phillips, J.D.; Hill, C.P.; McCoubrey, W.; Maines, M.D. Crystal structure of a biliverdin IXalpha reductase enzyme-cofactor complex. J. Mol. Biol., 2002, 319(5), 1199-1210.
[] [PMID: 12079357]
Kikuchi, G.; Yoshida, T. Heme degradation by the microsomal heme oxygenase system. Trends Biochem. Sci., 1980, 5, 323-325.
Montellano, P.R. The mechanism of heme oxygenase. Curr. Opin. Chem. Biol., 2000, 4(2), 221-227.
[] [PMID: 10742194]
Yoshida, T.; Migita, C.T. Mechanism of heme degradation by heme oxygenase. J. Inorg. Biochem., 2000, 82(1-4), 33-41.
[] [PMID: 11132636]
Matsui, T.; Unno, M.; Ikeda-Saito, M. Heme oxygenase reveals its strategy for catalyzing three successive oxygenation reactions. Acc. Chem. Res., 2010, 43(2), 240-247.
[] [PMID: 19827796]
Maines, M.D. Overview of heme degradation pathway. In: Curr. Protoc. Toxicol; , 2001; Chapter 9, . (Unit 9)
Stocker, R. Antioxidant activities of bile pigments. Antioxid. Redox Signal., 2004, 6(5), 841-849.
[PMID: 15345144]
Florczyk, U.M.; Jozkowicz, A.; Dulak, J. Biliverdin reductase: new features of an old enzyme and its potential therapeutic significance. Pharmacol. Rep., 2008, 60(1), 38-48.
[PMID: 18276984]
Hwang, H.W.; Lee, J.R.; Chou, K.Y.; Suen, C.S.; Hwang, M.J.; Chen, C.; Shieh, R.C.; Chau, L.Y. Oligomerization is crucial for the stability and function of heme oxygenase-1 in the endoplasmic reticulum. J. Biol. Chem., 2009, 284(34), 22672-22679.
[] [PMID: 19556236]
Abraham, N.G.; Drummond, G.S.; Lutton, J.D.; Kappas, A. The biological significance and physiological role of heme oxygenase. Cell. Physiol. Biochem., 1996, 6, 129-168.
Yoshida, T.; Noguchi, M.; Kikuchi, G. Oxygenated form of heme. heme oxygenase complex and requirement for second electron to initiate heme degradation from the oxygenated complex. J. Biol. Chem., 1980, 255(10), 4418-4420.
[PMID: 6892813]
Sun, J.; Wilks, A.; Ortiz de Montellano, P.R.; Loehr, T.M. Resonance Raman and EPR spectroscopic studies on heme-heme oxygenase complexes. Biochemistry, 1993, 32(51), 14151-14157.
[] [PMID: 8260499]
Takahashi, S.; Wang, J.; Rousseau, D.L.; Ishikawa, K.; Yoshida, T.; Host, J.R.; Ikeda-Saito, M. Heme-heme oxygenase complex. Structure of the catalytic site and its implication for oxygen activation. J. Biol. Chem., 1994, 269(2), 1010-1014.
[PMID: 8288555]
Migita, C.T.; Matera, K.M.; Ikeda-Saito, M.; Olson, J.S.; Fujii, H.; Yoshimura, T.; Zhou, H.; Yoshida, T. The oxygen and carbon monoxide reactions of heme oxygenase. J. Biol. Chem., 1998, 273(2), 945-949.
[] [PMID: 9422754]
Zhou, H.; Migita, C.T.; Sato, M.; Sun, D.; Zhang, X.; Ikeda-Saito, M.; Fujii, H.; Yoshida, T. Participation of carboxylate amino acid side chain in regiospecific oxidation of heme by heme oxygenase. J. Am. Chem. Soc., 2000, 122, 8311-8312.
Fujii, H.; Zhang, X.; Tomita, T.; Ikeda-Saito, M.; Yoshida, T. A role for highly conserved carboxylate, aspartate-140, in oxygen activation and heme degradation by heme oxygenase-1. J. Am. Chem. Soc., 2001, 123(27), 6475-6484.
[] [PMID: 11439033]
Lightning, L.K.; Huang, H.; Moenne-Loccoz, P.; Loehr, T.M.; Schuller, D.J.; Poulos, T.L.; de Montellano, P.R. Disruption of an active site hydrogen bond converts human heme oxygenase-1 into a peroxidase. J. Biol. Chem., 2001, 276(14), 10612-10619.
[] [PMID: 11121422]
Schuller, D.J.; Wilks, A.; Ortiz de Montellano, P.; Poulos, T.L. Crystallization of recombinant human heme oxygenase-1. Protein Sci., 1998, 7(8), 1836-1838.
[] [PMID: 10082382]
Omata, Y.; Asada, S.; Sakamoto, H.; Fukuyama, K.; Noguchi, M. Crystallization and preliminary X-ray diffraction studies on the water soluble form of rat heme oxygenase-1 in complex with heme. Acta Crystallogr. D Biol. Crystallogr., 1998, 54(Pt 5), 1017-1019.
[] [PMID: 9757125]
Schuller, D.J.; Wilks, A.; Ortiz de Montellano, P.R.; Poulos, T.L. Crystal structure of human heme oxygenase-1. Nat. Struct. Biol., 1999, 6(9), 860-867.
[] [PMID: 10467099]
Sugishima, M.; Omata, Y.; Kakuta, Y.; Sakamoto, H.; Noguchi, M.; Fukuyama, K. Crystal structure of rat heme oxygenase-1 in complex with heme. FEBS Lett., 2000, 471(1), 61-66.
[] [PMID: 10760513]
La Mar, G.N.; Asokan, A.; Espiritu, B.; Yeh, D.C.; Auclair, K.; Ortiz De Montellano, P.R. Solution 1H NMR of the active site of substrate-bound, cyanide-inhibited human heme oxygenase. comparison to the crystal structure of the water-ligated form. J. Biol. Chem., 2001, 276(19), 15676-15687.
[] [PMID: 11297521]
Li, Y.; Syvitski, R.T.; Chu, G.C.; Ikeda-Saito, M.; La Mar, G.N. Solution 1H NMR investigation of the active site molecular and electronic structures of the substrate-bound, cyanide-inhibited HmuO, a bacterial heme oxygenase from C. diphtheriae. J. Biol. Chem., 2003, 278(9), 6651-6663.
[] [PMID: 12480929]
Davydov, R.; Kofman, V.; Fujii, H.; Yoshida, T.; Ikeda-Saito, M.; Hoffman, B.M. Catalytic mechanism of heme oxygenase through EPR and ENDOR of cryoreduced oxy-heme oxygenase and its Asp 140 mutants. J. Am. Chem. Soc., 2002, 124(8), 1798-1808.
[] [PMID: 11853459]
Varfaj, F.; Lampe, J.N.; Ortiz de Montellano, P.R. Role of cysteine residues in heme binding to human heme oxygenase-2 elucidated by two-dimensional NMR spectroscopy. J. Biol. Chem., 2012, 287(42), 35181-35191.
[] [PMID: 22923613]
Bianchetti, C.M.; Yi, L.; Ragsdale, S.W.; Phillips, G.N.Jr. Comparison of apo- and heme-bound crystal structures of a truncated human heme oxygenase-2. J. Biol. Chem., 2007, 282(52), 37624-37631.
[] [PMID: 17965015]
Sugishima, M.; Sakamoto, H.; Kakuta, Y.; Omata, Y.; Hayashi, S.; Noguchi, M.; Fukuyama, K. Crystal structure of rat apo-heme oxygenase-1 (HO-1): mechanism of heme binding in HO-1 inferred from structural comparison of the apo and heme complex forms. Biochemistry, 2002, 41(23), 7293-7300.
[] [PMID: 12044160]
Lad, L.; Schuller, D.J.; Shimizu, H.; Friedman, J.; Li, H.; Ortiz de Montellano, P.R.; Poulos, T.L. Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1. J. Biol. Chem., 2003, 278(10), 7834-7843.
[] [PMID: 12500973]
Unno, M.; Ardèvol, A.; Rovira, C.; Ikeda-Saito, M. Structures of the substrate-free and product-bound forms of HmuO, a heme oxygenase from corynebacterium diphtheriae: x-ray crystallography and molecular dynamics investigation. J. Biol. Chem., 2013, 288(48), 34443-34458.
[] [PMID: 24106279]
Harada, E.; Sugishima, M.; Harada, J.; Fukuyama, K.; Sugase, K. Distal regulation of heme binding of heme oxygenase-1 mediated by conformational fluctuations. Biochemistry, 2015, 54(2), 340-348.
[] [PMID: 25496210]
Sugishima, M.; Moffat, K.; Noguchi, M. Discrimination between CO and O(2) in heme oxygenase: comparison of static structures and dynamic conformation changes following CO photolysis. Biochemistry, 2012, 51(43), 8554-8562.
[] [PMID: 23043644]
Takahashi, S.; Ishikawa, K.; Takeuchi, N.; Ikeda-Saito, M.; Yoshida, T.; Rousseau, D.L. Oxygen-bound heme-heme oxygenase complex: evidence for a highly bent structure of the cooridnated oxygen. J. Am. Chem. Soc., 1995, 117, 6002-6006.
Unno, M.; Matsui, T.; Chu, G.C.; Couture, M.; Yoshida, T.; Rousseau, D.L.; Olson, J.S.; Ikeda-Saito, M. Crystal structure of the dioxygen-bound heme oxygenase from Corynebacterium diphtheriae: implications for heme oxygenase function. J. Biol. Chem., 2004, 279(20), 21055-21061.
[] [PMID: 14966119]
Sugishima, M.; Sakamoto, H.; Noguchi, M.; Fukuyama, K. Crystal structures of ferrous and CO-, CN(-)-, and NO-bound forms of rat heme oxygenase-1 (HO-1) in complex with heme: structural implications for discrimination between CO and O2 in HO-1. Biochemistry, 2003, 42(33), 9898-9905.
[] [PMID: 12924938]
Sugishima, M.; Sakamoto, H.; Higashimoto, Y.; Omata, Y.; Hayashi, S.; Noguchi, M.; Fukuyama, K. Crystal structure of rat heme oxygenase-1 in complex with heme bound to azide. Implication for regiospecific hydroxylation of heme at the alpha-meso carbon. J. Biol. Chem., 2002, 277(47), 45086-45090.
[] [PMID: 12235152]
Yamaoka, M.; Sugishima, M.; Noguchi, M.; Fukuyama, K.; Mizutani, Y. Protein dynamics of heme–heme oxygenase-1 complex following carbon monoxide dissociation. J. Raman Spectrosc., 2011, 42, 910-916.
Friedman, J.; Meharenna, Y.T.; Wilks, A.; Poulos, T.L. Diatomic ligand discrimination by the heme oxygenases from Neisseria meningitidis and Pseudomonas aeruginosa. J. Biol. Chem., 2007, 282(2), 1066-1071.
[] [PMID: 17095508]
Sugishima, M.; Sakamoto, H.; Noguchi, M.; Fukuyama, K. CO-trapping site in heme oxygenase revealed by photolysis of its co-bound heme complex: mechanism of escaping from product inhibition. J. Mol. Biol., 2004, 341(1), 7-13.
[] [PMID: 15312758]
Sakamoto, H.; Omata, Y.; Hayashi, S.; Harada, S.; Palmer, G.; Noguchi, M. The reactivity of alpha-hydroxyhaem and verdohaem bound to haem oxygenase-1 to dioxygen and sodium dithionite. Eur. J. Biochem., 2002, 269(21), 5231-5239.
[] [PMID: 12392555]
Sakamoto, H.; Omata, Y.; Palmer, G.; Noguchi, M. Ferric alpha-hydroxyheme bound to heme oxygenase can be converted to verdoheme by dioxygen in the absence of added reducing equivalents. J. Biol. Chem., 1999, 274(26), 18196-18200.
[] [PMID: 10373419]
Sakamoto, H.; Takahashi, K.; Higashimoto, Y.; Harada, S.; Palmer, G.; Noguchi, M. A kinetic study of the mechanism of conversion of alpha-hydroxyheme to verdoheme while bound to heme oxygenase. Biochem. Biophys. Res. Commun., 2005, 338(1), 578-583.
[] [PMID: 16154530]
Matsui, T.; Nakajima, A.; Fujii, H.; Matera, K.M.; Migita, C.T.; Yoshida, T.; Ikeda-Saito, M. O(2)- and H(2)O(2)-dependent verdoheme degradation by heme oxygenase: reaction mechanisms and potential physiological roles of the dual pathway degradation. J. Biol. Chem., 2005, 280(44), 36833-36840.
[] [PMID: 16115896]
Sato, H.; Higashimoto, Y.; Sakamoto, H.; Sugishima, M.; Shimokawa, C.; Harada, J.; Palmer, G.; Noguchi, M. Reduction of oxaporphyrin ring of CO-bound α-verdoheme complexed with heme oxygenase-1 by NADPH-cytochrome P450 reductase. J. Inorg. Biochem., 2011, 105(2), 289-296.
[] [PMID: 21194630]
Lad, L.; Ortiz de Montellano, P.R.; Poulos, T.L. Crystal structures of ferrous and ferrous-NO forms of verdoheme in a complex with human heme oxygenase-1: catalytic implications for heme cleavage. J. Inorg. Biochem., 2004, 98(11), 1686-1695.
[] [PMID: 15522396]
Sugishima, M.; Sakamoto, H.; Higashimoto, Y.; Noguchi, M.; Fukuyama, K. Crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron chelate. Conformational change of the distal helix during the heme cleavage reaction. J. Biol. Chem., 2003, 278(34), 32352-32358.
[] [PMID: 12794075]
Wang, M.; Roberts, D.L.; Paschke, R.; Shea, T.M.; Masters, B.S.; Kim, J.J. Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes. Proc. Natl. Acad. Sci. USA, 1997, 94(16), 8411-8416.
[] [PMID: 9237990]
Xia, C.; Hamdane, D.; Shen, A.L.; Choi, V.; Kasper, C.B.; Pearl, N.M.; Zhang, H.; Im, S.C.; Waskell, L.; Kim, J.J. Conformational changes of NADPH-cytochrome P450 oxidoreductase are essential for catalysis and cofactor binding. J. Biol. Chem., 2011, 286(18), 16246-16260.
[] [PMID: 21345800]
Huang, W.C.; Ellis, J.; Moody, P.C.; Raven, E.L.; Roberts, G.C. Redox-linked domain movements in the catalytic cycle of cytochrome p450 reductase. Structure, 2013, 21(9), 1581-1589.
[] [PMID: 23911089]
Pudney, C.R.; Khara, B.; Johannissen, L.O.; Scrutton, N.S. Coupled motions direct electrons along human microsomal P450 Chains. PLoS Biol., 2011, 9(12), e1001222
[] [PMID: 22205878]
Jenner, M.; Ellis, J.; Huang, W.C.; Lloyd Raven, E.; Roberts, G.C.; Oldham, N.J. Detection of a protein conformational equilibrium by electrospray ionisation-ion mobility-mass spectrometry. Angew. Chem. Int. Ed. Engl., 2011, 50(36), 8291-8294.
[] [PMID: 21688358]
Hamdane, D.; Xia, C.; Im, S.C.; Zhang, H.; Kim, J.J.; Waskell, L. Structure and function of an NADPH-cytochrome P450 oxidoreductase in an open conformation capable of reducing cytochrome P450. J. Biol. Chem., 2009, 284(17), 11374-11384.
[] [PMID: 19171935]
Sugishima, M.; Sato, H.; Higashimoto, Y.; Harada, J.; Wada, K.; Fukuyama, K.; Noguchi, M. Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase. Proc. Natl. Acad. Sci. USA, 2014, 111(7), 2524-2529.
[] [PMID: 24550278]
Higashimoto, Y.; Sakamoto, H.; Hayashi, S.; Sugishima, M.; Fukuyama, K.; Palmer, G.; Noguchi, M. Involvement of NADPH in the interaction between heme oxygenase-1 and cytochrome P450 reductase. J. Biol. Chem., 2005, 280(1), 729-737.
[] [PMID: 15516695]
Higashimoto, Y.; Sugishima, M.; Sato, H.; Sakamoto, H.; Fukuyama, K.; Palmer, G.; Noguchi, M. Mass spectrometric identification of lysine residues of heme oxygenase-1 that are involved in its interaction with NADPH-cytochrome P450 reductase. Biochem. Biophys. Res. Commun., 2008, 367(4), 852-858.
[] [PMID: 18194664]
Higashimoto, Y.; Sato, H.; Sakamoto, H.; Takahashi, K.; Palmer, G.; Noguchi, M. The reactions of heme- and verdoheme-heme oxygenase-1 complexes with FMN-depleted NADPH-cytochrome P450 reductase. Electrons required for verdoheme oxidation can be transferred through a pathway not involving FMN. J. Biol. Chem., 2006, 281(42), 31659-31667.
[] [PMID: 16928691]
Fukuyama, K. Structure and function of plant-type ferredoxins. Photosynth. Res., 2004, 81(3), 289-301.
[] [PMID: 16034533]
Aoki, R.; Goto, T.; Fujita, Y. A heme oxygenase isoform is essential for aerobic growth in the cyanobacterium Synechocystis sp. PCC 6803: modes of differential operation of two isoforms/enzymes to adapt to low oxygen environments in cyanobacteria. Plant Cell Physiol., 2011, 52(10), 1744-1756.
[] [PMID: 21828104]
Cornejo, J.; Beale, S.I. Phycobilin biosynthetic reactions in extracts of cyanobacteria. Photosynth. Res., 1997, 51, 223-230.
Cornejo, J.; Willows, R.D.; Beale, S.I. Phytobilin biosynthesis: cloning and expression of a gene encoding soluble ferredoxin-dependent heme oxygenase from Synechocystis sp. PCC 6803. Plant J., 1998, 15(1), 99-107.
[] [PMID: 9744099]
Sugishima, M.; Hagiwara, Y.; Zhang, X.; Yoshida, T.; Migita, C.T.; Fukuyama, K. Crystal structure of dimeric heme oxygenase-2 from Synechocystis sp. PCC 6803 in complex with heme. Biochemistry, 2005, 44(11), 4257-4266.
[] [PMID: 15766254]
Sugishima, M.; Migita, C.T.; Zhang, X.; Yoshida, T.; Fukuyama, K. Crystal structure of heme oxygenase-1 from cyanobacterium Synechocystis sp. PCC 6803 in complex with heme. Eur. J. Biochem., 2004, 271(22), 4517-4525.
[] [PMID: 15560792]
Schuller, D.J.; Zhu, W.; Stojiljkovic, I.; Wilks, A.; Poulos, T.L. Crystal structure of heme oxygenase from the gram-negative pathogen Neisseria meningitidis and a comparison with mammalian heme oxygenase-1. Biochemistry, 2001, 40(38), 11552-11558.
[] [PMID: 11560504]
Hirotsu, S.; Chu, G.C.; Unno, M.; Lee, D.S.; Yoshida, T.; Park, S.Y.; Shiro, Y.; Ikeda-Saito, M. The crystal structures of the ferric and ferrous forms of the heme complex of HmuO, a heme oxygenase of Corynebacterium diphtheriae. J. Biol. Chem., 2004, 279(12), 11937-11947.
[] [PMID: 14645223]
Friedman, J.; Lad, L.; Li, H.; Wilks, A.; Poulos, T.L. Structural basis for novel delta-regioselective heme oxygenation in the opportunistic pathogen Pseudomonas aeruginosa. Biochemistry, 2004, 43(18), 5239-5245.
[] [PMID: 15122889]
Unno, M.; Matsui, T.; Ikeda-Saito, M. Structure and catalytic mechanism of heme oxygenase. Nat. Prod. Rep., 2007, 24(3), 553-570.
[] [PMID: 17534530]
Unno, M.; Matsui, T.; Ikeda-Saito, M. Crystallographic studies of heme oxygenase complexed with an unstable reaction intermediate, verdoheme. J. Inorg. Biochem., 2012, 113, 102-109.
[] [PMID: 22673156]
Maines, M.D. Zinc. protoporphyrin is a selective inhibitor of heme oxygenase activity in the neonatal rat. Biochim. Biophys. Acta, 1981, 673(3), 339-350.
[] [PMID: 6894392]
Vlahakis, J.Z.; Kinobe, R.T.; Bowers, R.J.; Brien, J.F.; Nakatsu, K.; Szarek, W.A. Synthesis and evaluation of azalanstat analogues as heme oxygenase inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(5), 1457-1461.
[] [PMID: 15713406]
Kinobe, R.T.; Vlahakis, J.Z.; Vreman, H.J.; Stevenson, D.K.; Brien, J.F.; Szarek, W.A.; Nakatsu, K. Selectivity of imidazole-dioxolane compounds for in vitro inhibition of microsomal haem oxygenase isoforms. Br. J. Pharmacol., 2006, 147(3), 307-315.
[] [PMID: 16331285]
Vlahakis, J.Z.; Kinobe, R.T.; Bowers, R.J.; Brien, J.F.; Nakatsu, K.; Szarek, W.A. Imidazole-dioxolane compounds as isozyme-selective heme oxygenase inhibitors. J. Med. Chem., 2006, 49(14), 4437-4441.
[] [PMID: 16821802]
Sugishima, M.; Higashimoto, Y.; Oishi, T.; Takahashi, H.; Sakamoto, H.; Noguchi, M.; Fukuyama, K. X-ray crystallographic and biochemical characterization of the inhibitory action of an imidazole-dioxolane compound on heme oxygenase. Biochemistry, 2007, 46(7), 1860-1867.
[] [PMID: 17253780]
Rahman, M.N.; Vukomanovic, D.; Vlahakis, J.Z.; Szarek, W.A.; Nakatsu, K.; Jia, Z. Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds. J. R. Soc. Interface, 2013, 10(78), 20120697
[] [PMID: 23097500]
Rahman, M.N.; Vlahakis, J.Z.; Vukomanovic, D.; Lee, W.; Szarek, W.A.; Nakatsu, K.; Jia, Z. A novel, “double-clamp” binding mode for human heme oxygenase-1 inhibition. PLoS One, 2012, 7(1), e29514
[] [PMID: 22276118]
Rahman, M.N.; Vlahakis, J.Z.; Roman, G.; Vukomanovic, D.; Szarek, W.A.; Nakatsu, K.; Jia, Z. Structural characterization of human heme oxygenase-1 in complex with azole-based inhibitors. J. Inorg. Biochem., 2010, 104(3), 324-330.
[] [PMID: 19917515]
Rahman, M.N.; Vlahakis, J.Z.; Vukomanovic, D.; Szarek, W.A.; Nakatsu, K.; Jia, Z. X-ray crystal structure of human heme oxygenase-1 with (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: a novel, inducible binding mode. J. Med. Chem., 2009, 52(15), 4946-4950.
[] [PMID: 19601578]
Rahman, M.N.; Vlahakis, J.Z.; Szarek, W.A.; Nakatsu, K.; Jia, Z. X-ray crystal structure of human heme oxygenase-1 in complex with 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone: a common binding mode for imidazole-based heme oxygenase-1 inhibitors. J. Med. Chem., 2008, 51(19), 5943-5952.
[] [PMID: 18798608]
Matsui, T.; Iwasaki, M.; Sugiyama, R.; Unno, M.; Ikeda-Saito, M. Dioxygen activation for the self-degradation of heme: reaction mechanism and regulation of heme oxygenase. Inorg. Chem., 2010, 49(8), 3602-3609.
[] [PMID: 20380462]
Noguchi, M.; Yoshida, T.; Kikuchi, G. , 1979, Purification and properties of biliverdin reductases from pig spleen and rat liver. J. Biochem., 1979, 86(4), 833-848.
[] [PMID: 40968]
Kutty, R.K.; Maines, M.D. Purification and characterization of biliverdin reductase from rat liver. J. Biol. Chem., 1981, 256(8), 3956-3962.
[PMID: 7217067]
Maines, M.D.; Trakshel, G.M. Purification and characterization of human biliverdin reductase. Arch. Biochem. Biophys., 1993, 300(1), 320-326.
[] [PMID: 8424666]
Yamaguchi, T.; Yamaguchi, N.; Nakajima, H.; Komoda, Y.; Ishikawa, M. Separation and identification of the isomers of biliverdin-IX and biliverdin-IX dimethyl ester by means of high performance liquid chromatography. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 1978, 55, 84-88.
Ahmed, F.H.; Mohamed, A.E.; Carr, P.D.; Lee, B.M.; Condic-Jurkic, K.; O’Mara, M.L.; Jackson, C.J. Rv2074 is a novel F420 H2 -dependent biliverdin reductase in Mycobacterium tuberculosis. Protein Sci., 2016, 25(9), 1692-1709.
[] [PMID: 27364382]
Franklin, E.; Browne, S.; Hayes, J.; Boland, C.; Dunne, A.; Elliot, G.; Mantle, T.J. Activation of biliverdin-IXalpha reductase by inorganic phosphate and related anions. Biochem. J., 2007, 405(1), 61-67.
[] [PMID: 17402939]
Sun, D.; Sato, M.; Yoshida, T.; Shimizu, H.; Miyatake, H.; Adachi, S.; Shiro, Y.; Kikuchi, A. Crystallization and preliminary X-ray diffraction analysis of a rat biliverdin reductase. Acta Crystallogr. D Biol. Crystallogr., 2000, 56(Pt 9), 1180-1182.
[] [PMID: 10957639]
Watanabe, A.; Hirata, K.; Hagiwara, Y.; Yutani, Y.; Sugishima, M.; Yamamoto, M.; Fukuyama, K.; Wada, K. Expression, purification and preliminary X-ray crystallographic analysis of cyanobacterial biliverdin reductase. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 2011, 67(Pt 3), 313-317.
[] [PMID: 21393834]
Takao, H.; Hirabayashi, K.; Nishigaya, Y.; Kouriki, H.; Nakaniwa, T.; Hagiwara, Y.; Harada, J.; Sato, H.; Yamazaki, T.; Sakakibara, Y.; Suiko, M.; Asada, Y.; Takahashi, Y.; Yamamoto, K.; Fukuyama, K.; Sugishima, M.; Wada, K. A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity. Nat. Commun., 2017, 8, 14397.
[] [PMID: 28169272]
Ahmad, Z.; Salim, M.; Maines, M.D. Human biliverdin reductase is a leucine zipper-like DNA-binding protein and functions in transcriptional activation of heme oxygenase-1 by oxidative stress. J. Biol. Chem., 2002, 277(11), 9226-9232.
[] [PMID: 11773068]
Salim, M.; Brown-Kipphut, B.A.; Maines, M.D. Human biliverdin reductase is autophosphorylated, and phosphorylation is required for bilirubin formation. J. Biol. Chem., 2001, 276(14), 10929-10934.
[] [PMID: 11278740]
Maines, M.D.; Ewing, J.F.; Huang, T.J.; Panahian, N. Nuclear localization of biliverdin reductase in the rat kidney: response to nephrotoxins that induce heme oxygenase-1. J. Pharmacol. Exp. Ther., 2001, 296(3), 1091-1097.
[PMID: 11181945]

© 2022 Bentham Science Publishers | Privacy Policy