吡啶核苷酸转氢酶的结构及功能

赵旵军,黄恩启,龚仁敏,朱国萍

中国生物化学与分子生物学报 ›› 2007, Vol. 23 ›› Issue (10) : 797-803.

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中国生物化学与分子生物学报 ›› 2007, Vol. 23 ›› Issue (10) : 797-803.
综述

吡啶核苷酸转氢酶的结构及功能

  • 赵旵军, 黄恩启, 龚仁敏, 朱国萍*
作者信息 +

Structure and Function of Pyridine Nucleotide Transhydrogenases

  • ZHAO Han-Jun, HUANG En-Qi, GONG Ren-Min, ZHU Guo-Ping*
Author information +
文章历史 +

摘要

吡啶核苷酸转氢酶(pyridine nucleotide transhydrogenases)是能直接催化NADP(H)与NAD(H)之间氢负离子可逆转移的氧化还原酶, 主要调控分解代谢和合成代谢过程中NADH与NADPH之间的动态平衡. 膜结合吡啶核苷酸转氢酶(TH)是ATP依赖性跨膜蛋白, 由2个亚基构成, 每个亚基包含dⅠ、dⅡ和dⅢ三个结构域. 在TH结合可变催化机制中, 氢负离子的转移总是与质子转移相偶联. 可溶性吡啶核苷酸转氢酶(STH)是非能量依赖性的黄素蛋白, 以可溶性多聚体形式存在. 目前认为,很多因活性氧自由基异常增多而引起的线粒体疾病都与TH的活性有关, 包括糖尿病、癌症、神经退行性疾病及心血管疾病等. TH分子机制的研究将有助于揭示这些线粒体疾病的致病机理以及为其诊断和基因治疗提供分子依据. STH作用机理的研究及其在辅酶再生系统中的应用, 将会推动代谢工程和工业生物催化过程的进一步发展.

Abstract

Pyridine nucleotide transhydrogenases are the redox enzymes for directly catalyzing the reversible hydride transfer between NAD(H) and NADP(H), where they regulate and restore the homeostasis of those two redox cofactors in catabolism and anabolism. The membranebound pyridine nucleotide transhydrogenase (TH), ATPlinked transmembrane protein, is composed of two subunits, each of which contains three domains (dⅠ, dⅡ and dⅢ). TH drives the transfer of hydride from NADH to NADP+ coupled with transmembrane proton import via bindingchange catalytic mechanism. The soluble pyridine nucleotide transhydrogenase (STH) is energyindependent flavoprotein and form remarkably large polymers. Recently, it is considered that many mitochondrial diseases and cell damage caused by mitochondrial reactive oxygen species are related to TH activities, including diabetes, cancer, neurodegenerative diseases, cardiovascular diseases, and also apoptosis and aging. To investigate the molecular mechanism of TH may reveal the pathogenic mechanism of mitochondrial diseases and provide the molecular basis for diagnosis and gene therapy. Research of mechanism and utilization of STH in cofactor regenerating system may promote the further development of metabolic engineering and industrial biocatalysis process.

关键词

膜结合转氢酶 / 可溶性转氢酶 / 分子机理 / 线粒体疾病 / 辅酶再生

Key words

Membrane-bound transhydrogenase / soluble transhydrogenase / molecular mechanism / mitochondrial diseases / cofactor regeneration

引用本文

导出引用
赵旵军,黄恩启,龚仁敏,朱国萍. 吡啶核苷酸转氢酶的结构及功能[J]. 中国生物化学与分子生物学报, 2007, 23(10): 797-803
ZHAOHan-Jun,HUANGEn-Qi,GONGRen-Min,ZHUGuo-Ping. Structure and Function of Pyridine Nucleotide Transhydrogenases[J]. Chinese Journal of Biochemistry and Molecular Biology, 2007, 23(10): 797-803

参考文献

[1] RydstrM J. Mitochondrial NADPH, transhydrogenase and disease[J]. Biochim Biophys Acta, 2006, 1757(5-6):721-726
[2] Toye A A, Lippiat J D, Proks P, et al. A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice[J]. Diabetologia, 2005, 48(4):675-686
[3] RydstrM J. Mitochondrial transhydrogenasea key enzyme in insulin secretion and, potentially, diabetes [J]. Trends Biochem Sci, 2006, 31(7):355-358
[4] Sánchez A M, Andrews J, Hussein I, et al. Effect of overexpression of a soluble pyridine nucleotide transhydrogenase (UdhA) on the production of poly (3-hydroxybutyrate) in Escherichia coli[J]. Biotechnol Prog, 2006, 22(2):420-425
[5] Ichinose H, Kamiya N, Goto M. Enzymatic redox cofactor regeneration in organic media: functionalization and application of glycerol dehydrogenase and soluble transhydrogenase in reverse micelles[J]. Biotechnol Prog, 2005, 21(4):1192-1197
[6] Bizouarn T, van Boxel G I, Bhakta T, et al. Nucleotide binding affinities of the intact protontranslocating transhydrogenase from Escherichia coli[J]. Biochim Biophys Acta, 2005, 1708(3):404-410
[7] Bizouarn T, Althage M, Pedersen A, et al. The organization of the membrane domain and its interaction with the NADP(H) binding site in protontranslocating transhydrogenase from E.coli[J]. Biochim Biophys Acta, 2002, 1555(1-3):122-127
[8] Whitehead S J, Rossington K E, Hafiz A, et al. Zinc ions selectively inhibit steps associated with binding and release of NADP(H) during turnover of protontranslocating transhydrogenase[J]. FEBS Lett, 2005, 579(13):2863-2867
[9] Boonstra B, French C E, Wainwright I, et al. The udhA gene of Escherichia coli encodes a soluble pyridine nucleotide transhydrogenase[J]. Bacteriology, 1999, 181(3):1030-1034
[10] Boonstra B, Rathbone D A, French C E, et al. Cofactor regeneration by a soluble pyridine nucleotide transhydrogenase for biological production of hydromorphone[J]. Appl Environ Microbiol, 2000, 66(12):5161-5166
[11] Johansson C, Pedersen A, Karlsson B G, et al. Redoxsensitive loops D and E regulate NADP(H) binding in domain Ⅲ and domain Ⅰdomain Ⅲ interactions in protontranslocating Escherichia coli transhydrogenase[J]. Eur J Biochem, 2002, 269(18):4505-4515
[12] Buckley PA, Jackson J B, Schneider T, et al. Proteinprotein recognition, hydride transfer and proton pumping in the transhydrogenase complex[J]. Structure, 2000, 8:809-815
[13] Broos J, Gabellieri E, van Boxel G I, et al. Tryptophan phosphorescence spectroscopy reveals that a domain in the NAD(H) binding component (dⅠ) of transhydrogenase from Rhodospirillum rubrum has an extremely rigid and conformationally homogeneous protein core[J]. J Biol Chem, 2003, 278(48):47578-47584
[14] Mather O C, Singh A, van Boxel G I, et al. Activesite conformational changes associated with hydride transfer in protontranslocating transhydrogenase[J]. Biochemistry, 2004, 43(34):10952-10964
[15] Johansson T, Oswald C, Pedersen A, et al. Xray structure of domain I of the protonpumping membrane protein transhydrogenase from Escherichia coli[J]. J Mol Biol, 2005, 352(2):299-312
[16] Yamaguchi M, Stout C D, Hatefi Y. The proton channel of the energytransducing nicotinamide nucleotide transhydrogenase of Escherichia coli[J]. J Biol Chem, 2002, 277(37):33670-33675
[17] Weston C J, White S A, Jackson J B. The unusual transhydrogenase of Entamoeba histolytica[J]. FEBS Lett, 2001, 488(1-2):51-54
[18] Wilson R, Obiozo U M, Quirk P G, et al. A hybrid of the transhydrogenases from Rhodospirillum rubrum and Mycobacterium tuberculosis catalyses rapid hydride transfer but not the complete, protontranslocating reaction [J]. Biochim Biophys Acta, 2006, 1757(3):215-223
[19] Jackson J B, White S A, Quirk P G, et al. The alternating site, binding change mechanism for proton translocation by transhydrogenase[J]. Biochemistry, 2002, 41(13):4173-4185
[20] Bizouarn T, Fjellstrm O, Axelsson M, et al. Interactions between the soluble domain I of nicotinamide nucleotide transhydrogenase from Rhodospirillum rubrum and transhydrogenase from Escherichia coli: Effects on catalytic and H+pumping activities[J]. Eur J Biochem, 2000, 267(11):3281-3288
[21] Sundaresan V, Yamaguchi M, Chartron J, et al. Conformational change in the NADP(H) binding domain of transhydrogenase defines four states[J]. Biochemistry, 2003, 42(42):12143-12153
[22] Yamaguchi M, Stout C D. Essential glycine in the proton channel of Escherichia coli transhydrogenase [J]. J Biol Chem, 2003, 278(46):45333-45339
[23] Boonstra B, Bjorklund L, French C E, et al. Cloning of the sth gene from Azotobacther vinelandii and costruction of chimeric soluble pyridine nucleotide transhydrogenase[J]. FEMS Microbiol Lett, 2000, 191(1):87-93
[24] Jackson J B. Proton translocation by transhydrogenase[J]. FEBS Lett, 2003, 545(1):18-24
[25] Cotton N P J, White S A, Peake S J, et al. The crystal structure of an asymmetric complex of the two nucleotide binding components of protontranslocating transhydrogenase[J]. Structure, 2001, 9(2):165-176
[26] Brondijk T H C, van Boxel G I, Mather O C, et al. The role of invariant amino acid residues at the hydride transfer site of protontranslocating transhydrogenase[J]. J Biol Chem, 2006, 281(19):13345-13354
[27] White S A, Peake S J, McSweeney S, et al. The highresolution structure of the NADP(H)binding component (dⅢ) of protontranslocating transhydrogenase from human heart mitochondria[J]. Structure, 2000, 8(1):1-12
[28] Sauer U, Canonaco F, Heri S, et al. The soluble and membranebound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli[J]. J Biol Chem, 2004, 279(8):6613-6619
[29] Zhu G P, Golding G B, Dean A M. The selective cause of an ancient adaptation [J]. Science, 2005, 307(5713):1279-1282
[30] Lowell B B, Shulman G I. Mitochondrial dysfunction and type 2 diabetes[J]. Science, 2005, 307(5708):384-387
[31] Remedi M S, Nichols C G, Koster J C. The mitochondria and insulin release: Nnt just a passing relationship [J]. Cell Metab, 2006, 3(1):5-7
[32] Freeman H, Shimomura K, Cox R D, et al. Nicotinamide nucleotide transhydrogenase: a link between insulin secretion, glucose metabolism and oxidative stress[J]. Biochem Soc Trans, 2006, 34(pt5):806-810
[33] Freeman H, Shimomura K, Horner E, et al. Nicotinamide nucleotide transhydrogenase: a key role in insulin secretion[J]. Cell Metab, 2006, 3(1):35-45
[34] Freeman H C, Hugill A, Dear N T, et al. Deletion of nicotinamide nucleotide transhydrogenase: a new quantitive trait locus accounting for glucose intolerance in C57BL/6J Mice[J]. Diabetes, 2006, 55(7):2153-2156
[35] Arkblad E L, Tuck S, Pestov N B, et al. A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress[J]. Free Radic Biol Med, 2005, 38(11):1518-1525
[36] Wallace D C. A mitochondrial paradigm of metabolic and degenerative diseases, aging and cancer: a dawn for evolutionary medicine[J]. Annu Rev Genet, 2005, 39:359-407
[37] Lin M T , Beal M F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases [J]. Nature, 2006, 443(7113):787-795
[38] Canonaco F, Hess T A, Heri S, et al. Metabolic flux response to phosphoglucose isomerase knockout in Escherichia coli and impact of overexpression of the soluble transhydrogenase UdhA[J]. FEMS Microbiol Lett, 2001, 204(2):247-252
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