1v5h › Citations

Structural basis of human cytoglobin for ligand binding.

Sugimoto H, Makino M, Sawai H, Kawada N, Yoshizato K, Shiro Y
J Mol Biol 339 873-85 (2004)
Cited: 73 times
EuropePMC logo PMID: 15165856

Abstract

Cytoglobin (Cgb), a newly discovered member of the vertebrate globin family, binds O(2) reversibly via its heme, as is the case for other mammalian globins (hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb)). While Cgb is expressed in various tissues, its physiological role is not clearly understood. Here, the X-ray crystal structure of wild type human Cgb in the ferric state at 2.4A resolution is reported. In the crystal structure, ferric Cgb is dimerized through two intermolecular disulfide bonds between Cys38(B2) and Cys83(E9), and the dimerization interface is similar to that of lamprey Hb and Ngb. The overall backbone structure of the Cgb monomer exhibits a traditional globin fold with a three-over-three alpha-helical sandwich, in which the arrangement of helices is basically the same among all globins studied to date. A detailed comparison reveals that the backbone structure of the CD corner to D helix region, the N terminus of the E-helix and the F-helix of Cgb resembles more closely those of pentacoordinated globins (Mb, lamprey Hb), rather than hexacoordinated globins (Ngb, rice Hb). However, the His81(E7) imidazole group coordinates directly to the heme iron as a sixth axial ligand to form a hexcoordinated heme, like Ngb and rice Hb. The position and orientation of the highly conserved residues in the heme pocket (Phe(CD1), Val(E11), distal His(E7) and proximal His(F8)) are similar to those of other globin proteins. Two alternative conformations of the Arg84(E10) guanidium group were observed, suggesting that it participates in ligand binding to Cgb, as is the case for Arg(E10) of Aplysia Mb and Lys(E10) of Ngb. The structural diversities and similarities among globin proteins are discussed with relevance to molecular evolutionary relationships.

Reviews - 1v5h mentioned but not cited (3)

  1. Regulation of Nitric Oxide Metabolism and Vascular Tone by Cytoglobin. Zweier JL, Ilangovan G. Antioxid Redox Signal 32 1172-1187 (2020)
  2. Role of cytoglobin, a novel radical scavenger, in stellate cell activation and hepatic fibrosis. Thuy LTT, Hai H, Kawada N. Clin Mol Hepatol 26 280-293 (2020)
  3. Simple mechanisms for the evolution of protein complexity. Pillai AS, Hochberg GKA, Thornton JW. Protein Sci 31 e4449 (2022)

Articles - 1v5h mentioned but not cited (4)

  1. Drug discovery using chemical systems biology: identification of the protein-ligand binding network to explain the side effects of CETP inhibitors. Xie L, Li J, Xie L, Bourne PE. PLoS Comput Biol 5 e1000387 (2009)
  2. Nitric-oxide dioxygenase function of human cytoglobin with cellular reductants and in rat hepatocytes. Gardner AM, Cook MR, Gardner PR. J Biol Chem 285 23850-23857 (2010)
  3. The effect of reactive oxygen and nitrogen species on the structure of cytoglobin: A potential tumor suppressor. De Backer J, Razzokov J, Hammerschmid D, Mensch C, Hafideddine Z, Kumar N, van Raemdonck G, Yusupov M, Van Doorslaer S, Johannessen C, Sobott F, Bogaerts A, Dewilde S. Redox Biol 19 1-10 (2018)
  4. Molecular Dynamics Simulation and Kinetic Study of Fluoride Binding to V21C/V66C Myoglobin with a Cytoglobin-like Disulfide Bond. Yin LL, Xu JK, Wang XJ, Gao SQ, Lin YW. Int J Mol Sci 21 E2512 (2020)


Reviews citing this publication (13)

  1. Disulfides as redox switches: from molecular mechanisms to functional significance. Wouters MA, Fan SW, Haworth NL. Antioxid Redox Signal 12 53-91 (2010)
  2. Function and evolution of vertebrate globins. Burmester T, Hankeln T. Acta Physiol (Oxf) 211 501-514 (2014)
  3. Role of the Gut-Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship. Ohtani N, Kawada N. Hepatol Commun 3 456-470 (2019)
  4. Cytoglobin: biochemical, functional and clinical perspective of the newest member of the globin family. Oleksiewicz U, Liloglou T, Field JK, Xinarianos G. Cell Mol Life Sci 68 3869-3883 (2011)
  5. Mammalian nerve globins in search of functions. Ascenzi P, Gustincich S, Marino M. IUBMB Life 66 268-276 (2014)
  6. Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia. Weiss MJ, Zhou S, Feng L, Gell DA, Mackay JP, Shi Y, Gow AJ. Ann N Y Acad Sci 1054 103-117 (2005)
  7. The heme environment of mouse neuroglobin: histidine imidazole plane orientations obtained from solution NMR and EPR spectroscopy as compared with X-ray crystallography. Walker FA. J Biol Inorg Chem 11 391-397 (2006)
  8. Discovery of cytoglobin and its roles in physiology and pathology of hepatic stellate cells. Yoshizato K, Thuy le TT, Shiota G, Kawada N. Proc Jpn Acad Ser B Phys Biol Sci 92 77-97 (2016)
  9. Redox and Peroxidase Activities of the Hemoglobin Superfamily: Relevance to Health and Disease. Reeder BJ. Antioxid Redox Signal 26 763-776 (2017)
  10. Cytoglobin as a Biomarker in Cancer: Potential Perspective for Diagnosis and Management. Bholah TC, Neergheen-Bhujun VS, Hodges NJ, Dyall SD, Bahorun T. Biomed Res Int 2015 824514 (2015)
  11. The role of globins in cardiovascular physiology. Keller TCS, Lechauve C, Keller AS, Brooks S, Weiss MJ, Columbus L, Ackerman H, Cortese-Krott MM, Isakson BE. Physiol Rev 102 859-892 (2022)
  12. Insights into the function of cytoglobin. Reeder BJ. Biochem Soc Trans 51 1907-1919 (2023)
  13. Ligand-Based Regulation of Dynamics and Reactivity of Hemoproteins. Turilli-Ghisolfi ES, Lualdi M, Fasano M. Biomolecules 13 683 (2023)

Articles citing this publication (53)

  1. Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin. Feng L, Gell DA, Zhou S, Gu L, Kong Y, Li J, Hu M, Yan N, Lee C, Rich AM, Armstrong RS, Lay PA, Gow AJ, Weiss MJ, Mackay JP, Shi Y. Cell 119 629-640 (2004)
  2. Cytoglobin overexpression protects against damage-induced fibrosis. Xu R, Harrison PM, Chen M, Li L, Tsui TY, Fung PC, Cheung PT, Wang G, Li H, Diao Y, Krissansen GW, Xu S, Farzaneh F. Mol Ther 13 1093-1100 (2006)
  3. Structure of oxidized alpha-haemoglobin bound to AHSP reveals a protective mechanism for haem. Feng L, Zhou S, Gu L, Gell DA, Mackay JP, Weiss MJ, Gow AJ, Shi Y. Nature 435 697-701 (2005)
  4. Promotion of liver and lung tumorigenesis in DEN-treated cytoglobin-deficient mice. Thuy le TT, Morita T, Yoshida K, Wakasa K, Iizuka M, Ogawa T, Mori M, Sekiya Y, Momen S, Motoyama H, Ikeda K, Yoshizato K, Kawada N. Am J Pathol 179 1050-1060 (2011)
  5. Gene cooption and convergent evolution of oxygen transport hemoglobins in jawed and jawless vertebrates. Hoffmann FG, Opazo JC, Storz JF. Proc Natl Acad Sci U S A 107 14274-14279 (2010)
  6. Cytoglobin conformations and disulfide bond formation. Lechauve C, Chauvierre C, Dewilde S, Moens L, Green BN, Marden MC, Célier C, Kiger L. FEBS J 277 2696-2704 (2010)
  7. Cytoglobin deficiency promotes liver cancer development from hepatosteatosis through activation of the oxidative stress pathway. Thuy le TT, Matsumoto Y, Thuy TT, Hai H, Suoh M, Urahara Y, Motoyama H, Fujii H, Tamori A, Kubo S, Takemura S, Morita T, Yoshizato K, Kawada N. Am J Pathol 185 1045-1060 (2015)
  8. Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver. Motoyama H, Komiya T, Thuy le TT, Tamori A, Enomoto M, Morikawa H, Iwai S, Uchida-Kobayashi S, Fujii H, Hagihara A, Kawamura E, Murakami Y, Yoshizato K, Kawada N. Lab Invest 94 192-207 (2014)
  9. Cytoglobin is a stress-responsive hemoprotein expressed in the developing and adult brain. Mammen PP, Shelton JM, Ye Q, Kanatous SB, McGrath AJ, Richardson JA, Garry DJ. J Histochem Cytochem 54 1349-1361 (2006)
  10. Absence of cytoglobin promotes multiple organ abnormalities in aged mice. Thuy le TT, Van Thuy TT, Matsumoto Y, Hai H, Ikura Y, Yoshizato K, Kawada N. Sci Rep 6 24990 (2016)
  11. Bishistidyl heme hexacoordination, a key structural property in Drosophila melanogaster hemoglobin. de Sanctis D, Dewilde S, Vonrhein C, Pesce A, Moens L, Ascenzi P, Hankeln T, Burmester T, Ponassi M, Nardini M, Bolognesi M. J Biol Chem 280 27222-27229 (2005)
  12. Hyperthermal stability of neuroglobin and cytoglobin. Hamdane D, Kiger L, Dewilde S, Uzan J, Burmester T, Hankeln T, Moens L, Marden MC. FEBS J 272 2076-2084 (2005)
  13. Conformational changes in redox pairs of protein structures. Fan SW, George RA, Haworth NL, Feng LL, Liu JY, Wouters MA. Protein Sci 18 1745-1765 (2009)
  14. Protection from intracellular oxidative stress by cytoglobin in normal and cancerous oesophageal cells. McRonald FE, Risk JM, Hodges NJ. PLoS One 7 e30587 (2012)
  15. Duplicated cytoglobin genes in teleost fishes. Fuchs C, Luckhardt A, Gerlach F, Burmester T, Hankeln T. Biochem Biophys Res Commun 337 216-223 (2005)
  16. Cytoglobin ligand binding regulated by changing haem-co-ordination in response to intramolecular disulfide bond formation and lipid interaction. Beckerson P, Wilson MT, Svistunenko DA, Reeder BJ. Biochem J 465 127-137 (2015)
  17. Disulfide bonds regulate binding of exogenous ligand to human cytoglobin. Tsujino H, Yamashita T, Nose A, Kukino K, Sawai H, Shiro Y, Uno T. J Inorg Biochem 135 20-27 (2014)
  18. Locally enhanced sampling molecular dynamics study of the dioxygen transport in human cytoglobin. Orlowski S, Nowak W. J Mol Model 13 715-723 (2007)
  19. Crystal structure of the carbon monoxide complex of human cytoglobin. Makino M, Sawai H, Shiro Y, Sugimoto H. Proteins 79 1143-1153 (2011)
  20. Pentacoordinate and hexacoordinate ferric hemes in acid medium: EPR, UV-Vis and CD studies of the giant extracellular hemoglobin of Glossoscolex paulistus. Marmo Moreira L, Lima Poli A, Costa-Filho AJ, Imasato H. Biophys Chem 124 62-72 (2006)
  21. Gene expression and tissue distribution of cytoglobin and myoglobin in the Amphibia and Reptilia: possible compensation of myoglobin with cytoglobin in skeletal muscle cells of anurans that lack the myoglobin gene. Xi Y, Obara M, Ishida Y, Ikeda S, Yoshizato K. Gene 398 94-102 (2007)
  22. Insights into hemoglobin assembly through in vivo mutagenesis of α-hemoglobin stabilizing protein. Khandros E, Mollan TL, Yu X, Wang X, Yao Y, D'Souza J, Gell DA, Olson JS, Weiss MJ. J Biol Chem 287 11325-11337 (2012)
  23. Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. Ascenzi P, Marino M, Polticelli F, Coletta M, Gioia M, Marini S, Pesce A, Nardini M, Bolognesi M, Reeder BJ, Wilson MT. Biochim Biophys Acta 1834 1750-1756 (2013)
  24. Possible Involvement of Nitric Oxide in Enhanced Liver Injury and Fibrogenesis during Cholestasis in Cytoglobin-deficient Mice. Van Thuy TT, Thuy LT, Yoshizato K, Kawada N. Sci Rep 7 41888 (2017)
  25. Reduction of the internal disulfide bond between Cys 38 and 83 switches the ligand migration pathway in cytoglobin. Astudillo L, Bernad S, Derrien V, Sebban P, Miksovska J. J Inorg Biochem 129 23-29 (2013)
  26. Hell's Gate globin I: an acid and thermostable bacterial hemoglobin resembling mammalian neuroglobin. Teh AH, Saito JA, Baharuddin A, Tuckerman JR, Newhouse JS, Kanbe M, Newhouse EI, Rahim RA, Favier F, Didierjean C, Sousa EH, Stott MB, Dunfield PF, Gonzalez G, Gilles-Gonzalez MA, Najimudin N, Alam M. FEBS Lett 585 3250-3258 (2011)
  27. Neuroglobin and cytoglobin: Two new entries in the hemoglobin superfamily*. Ascenzi P, Bocedi A, de Sanctis D, Pesce A, Bolognesi M, Marden MC, Dewilde S, Moens L, Hankeln T, Burmester T. Biochem Mol Biol Educ 32 305-313 (2004)
  28. Regulating the coordination state of a heme protein by a designed distal hydrogen-bonding network. Du JF, Li W, Li L, Wen GB, Lin YW, Tan X. ChemistryOpen 4 97-101 (2015)
  29. Selective overexpression of cytoglobin in stellate cells attenuates thioacetamide-induced liver fibrosis in mice. Thi Thanh Hai N, Thuy LTT, Shiota A, Kadono C, Daikoku A, Hoang DV, Dat NQ, Sato-Matsubara M, Yoshizato K, Kawada N. Sci Rep 8 17860 (2018)
  30. Identification of an intermolecular disulfide bond in barley hemoglobin. Bykova NV, Igamberdiev AU, Ens W, Hill RD. Biochem Biophys Res Commun 347 301-309 (2006)
  31. Cytoglobin has potent superoxide dismutase function. Zweier JL, Hemann C, Kundu T, Ewees MG, Khaleel SA, Samouilov A, Ilangovan G, El-Mahdy MA. Proc Natl Acad Sci U S A 118 e2105053118 (2021)
  32. Stagnation of histopathological improvement is a predictor of hepatocellular carcinoma development after hepatitis C virus eradication. Motoyama H, Tamori A, Kubo S, Uchida-Kobayashi S, Takemura S, Tanaka S, Ohfuji S, Teranishi Y, Kozuka R, Kawamura E, Hagihara A, Morikawa H, Enomoto M, Murakami Y, Kawada N. PLoS One 13 e0194163 (2018)
  33. Cytoglobin affects tumorigenesis and the expression of ulcerative colitis-associated genes under chemically induced colitis in mice. Yassin M, Kissow H, Vainer B, Joseph PD, Hay-Schmidt A, Olsen J, Pedersen AE. Sci Rep 8 6905 (2018)
  34. An intramolecular disulfide bond designed in myoglobin fine-tunes both protein structure and peroxidase activity. Wu LB, Yuan H, Zhou H, Gao SQ, Nie CM, Tan X, Wen GB, Lin YW. Arch Biochem Biophys 600 47-55 (2016)
  35. Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite. Dent MR, DeMartino AW, Tejero J, Gladwin MT. Inorg Chem 60 15918-15940 (2021)
  36. Regulation of both the structure and function by a de novo designed disulfide bond: a case study of heme proteins in myoglobin. Yin LL, Yuan H, Du KJ, He B, Gao SQ, Wen GB, Tan X, Lin YW. Chem Commun (Camb) 54 4356-4359 (2018)
  37. Solution 1H NMR characterization of the axial bonding of the two His in oxidized human cytoglobin. Bondarenko V, Dewilde S, Moens L, La Mar GN. J Am Chem Soc 128 12988-12999 (2006)
  38. Antarctic fish versus human cytoglobins - The same but yet so different. Cuypers B, Vermeylen S, Hammerschmid D, Trashin S, Rahemi V, Konijnenberg A, De Schutter A, Cheng CC, Giordano D, Verde C, De Wael K, Sobott F, Dewilde S, Van Doorslaer S. J Inorg Biochem 173 66-78 (2017)
  39. Dietary Iron Overload Abrogates Chemically-Induced Liver Cirrhosis in Rats. Atarashi M, Izawa T, Mori M, Inai Y, Kuwamura M, Yamate J. Nutrients 10 E1400 (2018)
  40. Stereochemistry of residues in turning regions of helical proteins. Kozak JJ, Gray HB. J Biol Inorg Chem 24 879-888 (2019)
  41. Cytoglobin deficiency potentiates Crb1-mediated retinal degeneration in rd8 mice. Kwon YS, Tham A, Lopez AJ, Edwards S, Woods S, Chen J, Wong-Fortunato J, Quiroz Alonso A, Javier S, Au I, Clarke M, Humpal D, Lloyd KCK, Thomasy S, Murphy C, Glaser TM, Moshiri A. Dev Biol 458 141-152 (2020)
  42. Molecular dynamics simulation of carboxy and deoxy human cytoglobin in solution. Zhang B, Xu J, Li Y, Du W, Fang W. J Inorg Biochem 105 949-956 (2011)
  43. Redox sensor properties of human cytoglobin allosterically regulate heme pocket reactivity. DeMartino AW, Amdahl MB, Bocian K, Rose JJ, Tejero J, Gladwin MT. Free Radic Biol Med 162 423-434 (2021)
  44. Regulation of nitrite reductase and lipid binding properties of cytoglobin by surface and distal histidine mutations. Kaliszuk SJ, Morgan NI, Ayers TN, Sparacino-Watkins CE, DeMartino AW, Bocian K, Ragireddy V, Tong Q, Tejero J. Nitric Oxide 125-126 12-22 (2022)
  45. Research Support, Non-U.S. Gov't Crystal structure of Kumaglobin: a hexacoordinated heme protein from an anhydrobiotic tardigrade, Ramazzottius varieornatus. Kim J, Fukuda Y, Inoue T. FEBS J 286 1287-1304 (2019)
  46. Dynamic features of carboxy cytoglobin distal mutants investigated by molecular dynamics simulations. Zhao C, Du W. J Biol Inorg Chem 21 251-261 (2016)
  47. Molecular characterization and expression changes of cytoglobin genes in response to hypoxia in a Tibetan schizothoracine fish, Schizopygopsis pylzovi. Chao Y, Xia M, Wu R, Chen Q, Zheng Z, Qi D. Fish Physiol Biochem 45 863-872 (2019)
  48. Redox control and autoxidation of class 1, 2 and 3 phytoglobins from Arabidopsis thaliana. Mot AC, Puscas C, Miclea P, Naumova-Letia G, Dorneanu S, Podar D, Dissmeyer N, Silaghi-Dumitrescu R. Sci Rep 8 13714 (2018)
  49. pH-dependent structural changes in haemoglobin component V from the midge larva Propsilocerus akamusi (Orthocladiinae, Diptera). Kuwada T, Hasegawa T, Takagi T, Sato I, Shishikura F. Acta Crystallogr D Biol Crystallogr 66 258-267 (2010)
  50. Effects of distal mutation on the dynamic properties of carboxycytoglobin: a molecular dynamics simulation study. Zhao C, Zhang B, Du W. J Biol Inorg Chem 18 947-955 (2013)
  51. Involvement of the distal Arg residue in Cl⁻ binding of midge larval haemoglobin. Kuwada T, Hasegawa T, Takagi T, Sakae T, Sato I, Shishikura F. Acta Crystallogr D Biol Crystallogr 67 488-495 (2011)
  52. Effect of Low Temperature on Globin Expression, Respiratory Metabolic Enzyme Activities, and Gill Structure of Litopenaeus vannamei. Wu M, Chen N, Huang CX, He Y, Zhao YZ, Chen XH, Chen XL, Wang HL. Biochemistry (Mosc) 82 844-851 (2017)
  53. Neuronal Cytoglobin in the Auditory Brainstem of Rat and Mouse: Distribution, Cochlear Projection, and Nitric Oxide Production. Reuss S, Balmaceda D, Elgurt M, Riemann R. Brain Sci 13 107 (2023)


Related citations provided by authors (1)

  1. Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans. Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y Biochemistry 42 5133-5142 (2003)

Quick links