Involvement of NADP(H) in the Interaction between Heme Oxygenase-1 and Cytochrome P450 Reductase

Higashimoto, Yuichiro; Sakamoto, Hiroshi; Hayashi, Shunsuke; Sugishima, Masakazu; Fukuyama, Keiichi; Palmer, Graham; Noguchi, Masato

doi:10.1074/jbc.m406203200

Cited by 39 publications

(71 citation statements)

References 68 publications

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“…This is similar to that seen in the docking model of the complex of HO-1 and CPR (Fig. 3B) as previously reported [16]. Interestingly, although lysine residues at positions 18, 22, 39, 149, 177 and 179 in rat HO-1 are located within 5 Å from BVR, they are not close to any acidic residues of BVR.…”

supporting

confidence: 90%

“…Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Recently, using site-specific mutation and docking modeling, we found that Arg-185 and Lys-149 of rat HO-1 are important in both the HO activity and its association with CPR [16]. In our model, the guanidino group of Arg-185 interacts electrostatically with 2′-phosphate of NADPH bound to CPR.…”

Section: Introductionmentioning

confidence: 76%

“…Recently, using site-specific mutation and docking modeling, we found that Arg-185 and Lys-149 of rat HO-1 are important in both the HO activity and its association with CPR [16]. In our model, the guanidino group of Arg-185 interacts electrostatically with 2′-phosphate of NADPH bound to CPR.…”

mentioning

confidence: 76%

“…The program Hex [23] was used to predict the structure of the complex of rat HO-1 (Protein Data Bank Code 1DVE) and rat BVR (Protein Data Bank Code 1GCU) as described previously [16].…”

Section: Computer Modelingmentioning

confidence: 99%

“…The purification of BVR from rat liver was carried out according to published procedures [3]. , and is known to stabilize the interaction between heme-rat HO-1 complex and CPR [16]. Acetylation of the lysine residues of the heme-rat HO-1 complex was carried out with 2 μl of 15 mM acetic anhydride (Nacalai Tesque, Japan) for 15 min on ice.…”

mentioning

confidence: 99%

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Mass spectrometric identification of lysine residues of heme oxygenase-1 that are involved in its interaction with NADPH-cytochrome P450 reductase

Higashimoto

Sugishima

Satō

et al. 2008

Biochemical and Biophysical Research Communications

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The lysine residues of rat heme oxygenase-1 (HO-1) were acetylated by acetic anhydride in the absence and presence of NADPH-cytochrome P450 reductase (CPR) or biliverdin reductase (BVR). Nine acetylated peptides were identified by MALDI-TOF mass spectrometry in the tryptic fragments obtained from HO-1 acetylated without the reductases (referred to as the fully acetylated HO-1). The presence of CPR prevented HO-1 from acetylation of lysine residues, Lys-149 and Lys-153, located in the F-helix. The heme degradation activity of the fully acetylated HO-1 in the NADPH/CPRsupported system was significantly reduced, whereas almost no inactivation was detected in HO-1 in the presence of CPR, which prevented acetylation of Lys-149 and Lys-153. On the other hand, the presence of BVR showed no protective effect on the acetylation of HO-1. The interaction of HO-1 with CPR or BVR is discussed based on the acetylation pattern and on molecular modeling. KeywordsHeme oxygenase; NADPH-cytochrome P450 reductase; biliverdin reductase; MALDI-TOF mass spectrometry; chemical modification; protein-protein interaction Heme oxygenase (HO, EC 1.14.99.3) is a membrane-bound microsomal enzyme that catalyzes the degradation of heme to biliverdin, carbon monoxide (CO), and free iron [1,2]. Biliverdin is subsequently converted to bilirubin by a soluble cytosolic enzyme, biliverdin IXα reductase (BVR, EC 1.2.1.24) [3]. The electrons required for HO catalysis in mammals are provided by NADPH-cytochrome P450 reductase (CPR, EC 1.6.2.4), a 78-kDa membrane-bound * Correspondence should be addressed to: Prof. Masato Noguchi, Department of Medical Biochemistry, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan, Tel.: +81-942-31-7544; fax: +81-942-31-4377. E-mail address: mnoguchi@med.kurume-u.ac.jp (M. Noguchi).Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Recently, using site-specific mutation and docking modeling, we found that Arg-185 and Lys-149 of rat HO-1 are important in both the HO activity and its association with CPR [16]. In our model, the guanidino group of Arg-185 interacts electrostatically with 2′-phosphate of NADPH bound to CPR. On the other hand, Lys-149 is close to the acidic amino acid clusters near the FMN binding site of CPR; mutation of the acidic clusters causes reduction of the electron transfer rates from CPR to cytochrome P450s [17]. Thus, Arg-185 and Lys-149 appear to interact with CPR in such a way as to orient the redox partners for optimal electron transfer from CPR to the heme of HO-1. The model also suggested that the electrons from CPR are ...

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supporting

confidence: 90%

Section: Introductionmentioning

confidence: 76%

mentioning

confidence: 76%

“…The program Hex [23] was used to predict the structure of the complex of rat HO-1 (Protein Data Bank Code 1DVE) and rat BVR (Protein Data Bank Code 1GCU) as described previously [16].…”

Section: Computer Modelingmentioning

confidence: 99%

mentioning

confidence: 99%

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Mass spectrometric identification of lysine residues of heme oxygenase-1 that are involved in its interaction with NADPH-cytochrome P450 reductase

Higashimoto

Sugishima

Satō

et al. 2008

Biochemical and Biophysical Research Communications

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Survey of the year 2005 commercial optical biosensor literature

2006

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We identified 1113 articles (103 reviews, 1010 primary research articles) published in 2005 that describe experiments performed using commercially available optical biosensors. While this number of publications is impressive, we find that the quality of the biosensor work in these articles is often pretty poor. It is a little disappointing that there appears to be only a small set of researchers who know how to properly perform, analyze, and present biosensor data. To help focus the field, we spotlight work published by 10 research groups that exemplify the quality of data one should expect to see from a biosensor experiment. Also, in an effort to raise awareness of the common problems in the biosensor field, we provide side-by-side examples of good and bad data sets from the 2005 literature.

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P450 Oxidoreductase Deficiency (PORD)

Flück¹,

Pandey²

2013

Genetic Steroid Disorders

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Involvement of NADP(H) in the Interaction between Heme Oxygenase-1 and Cytochrome P450 Reductase

Cited by 39 publications

References 68 publications

Mass spectrometric identification of lysine residues of heme oxygenase-1 that are involved in its interaction with NADPH-cytochrome P450 reductase

Mass spectrometric identification of lysine residues of heme oxygenase-1 that are involved in its interaction with NADPH-cytochrome P450 reductase

Survey of the year 2005 commercial optical biosensor literature

P450 Oxidoreductase Deficiency (PORD)

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