2vck Citations

Phycoerythrobilin synthase (PebS) of a marine virus. Crystal structures of the biliverdin complex and the substrate-free form.

J. Biol. Chem. 283 27547-54 (2008)
Related entries: 2vcl, 2vgr

Cited: 18 times
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The reddish purple open chain tetrapyrrole pigment phycoerythrobilin (PEB; A(lambdamax) approximately 550 nm) is an essential chromophore of the light-harvesting phycobiliproteins of most cyanobacteria, red algae, and cryptomonads. The enzyme phycoerythrobilin synthase (PebS), recently discovered in a marine virus infecting oceanic cyanobacteria of the genus Prochlorococcus (cyanophage PSSM-2), is a new member of the ferredoxin-dependent bilin reductase (FDBR) family. In a formal four-electron reduction, the substrate biliverdin IXalpha is reduced to yield 3Z-PEB, a reaction that commonly requires the action of two individual FDBRs. The first reaction catalyzed by PebS is the reduction of the 15,16-methine bridge of the biliverdin IXalpha tetrapyrrole system. This reaction is exclusive to PEB biosynthetic enzymes. The second reduction site is the A-ring 2,3,3(1),3(2)-diene system, the most common target of FDBRs. Here, we present the first crystal structures of a PEB biosynthetic enzyme. Structures of the substrate complex were solved at 1.8- and 2.1-A resolution and of the substrate-free form at 1.55-A resolution. The overall folding revealed an alpha/beta/alpha-sandwich with similarity to the structure of phycocyanobilin:ferredoxin oxidoreductase (PcyA). The substrate-binding site is located between the central beta-sheet and C-terminal alpha-helices. Eight refined molecules with bound substrate, from two different crystal forms, revealed a high flexibility of the substrate-binding pocket. The substrate was found to be either in a planar porphyrin-like conformation or in a helical conformation and is coordinated by a conserved aspartate/asparagine pair from the beta-sheet side. From the alpha-helix side, a conserved highly flexible aspartate/proline pair is involved in substrate binding and presumably catalysis.

Reviews citing this publication (3)

  1. Bacterial phytochromes: more than meets the light. Auldridge ME, Forest KT. Crit. Rev. Biochem. Mol. Biol. 46 67-88 (2011)
  2. The chloroplast proteome: a survey from the Chlamydomonas reinhardtii perspective with a focus on distinctive features. Terashima M, Specht M, Hippler M. Curr. Genet. 57 151-168 (2011)
  3. Phycobiliproteins in Prochlorococcus marinus: biosynthesis of pigments and their assembly into proteins. Wiethaus J, Busch AW, Dammeyer T, Frankenberg-Dinkel N. Eur. J. Cell Biol. 89 1005-1010 (2010)

Articles citing this publication (15)

  1. Structure of the biliverdin radical intermediate in phycocyanobilin:ferredoxin oxidoreductase identified by high-field EPR and DFT. Stoll S, Gunn A, Brynda M, Sughrue W, Kohler AC, Ozarowski A, Fisher AJ, Lagarias JC, Britt RD. J. Am. Chem. Soc. 131 1986-1995 (2009)
  2. Phycoerythrin-specific bilin lyase-isomerase controls blue-green chromatic acclimation in marine Synechococcus. Shukla A, Biswas A, Blot N, Partensky F, Karty JA, Hammad LA, Garczarek L, Gutu A, Schluchter WM, Kehoe DM. Proc. Natl. Acad. Sci. U.S.A. 109 20136-20141 (2012)
  3. Crystal structure of red chlorophyll catabolite reductase: enlargement of the ferredoxin-dependent bilin reductase family. Sugishima M, Kitamori Y, Noguchi M, Kohchi T, Fukuyama K. J. Mol. Biol. 389 376-387 (2009)
  4. Structural insights into vinyl reduction regiospecificity of phycocyanobilin:ferredoxin oxidoreductase (PcyA). Hagiwara Y, Sugishima M, Khawn H, Kinoshita H, Inomata K, Shang L, Lagarias JC, Takahashi Y, Fukuyama K. J. Biol. Chem. 285 1000-1007 (2010)
  5. Electrostatic interaction of phytochromobilin synthase and ferredoxin for biosynthesis of phytochrome chromophore. Chiu FY, Chen YR, Tu SL. J. Biol. Chem. 285 5056-5065 (2010)
  6. Broad host range vectors for expression of proteins with (Twin-) Strep-tag, His-tag and engineered, export optimized yellow fluorescent protein. Dammeyer T, Timmis KN, Tinnefeld P. Microb. Cell Fact. 12 49 (2013)
  7. Crystal structures of the substrate-bound forms of red chlorophyll catabolite reductase: implications for site-specific and stereospecific reaction. Sugishima M, Okamoto Y, Noguchi M, Kohchi T, Tamiaki H, Fukuyama K. J. Mol. Biol. 402 879-891 (2010)
  8. Structural and mechanistic insight into the ferredoxin-mediated two-electron reduction of bilins. Busch AW, Reijerse EJ, Lubitz W, Frankenberg-Dinkel N, Hofmann E. Biochem. J. 439 257-264 (2011)
  9. Structural basis for hydration dynamics in radical stabilization of bilin reductase mutants. Kohler AC, Gae DD, Richley MA, Stoll S, Gunn A, Lim S, Martin SS, Doukov TI, Britt RD, Ames JB, Lagarias JC, Fisher AJ. Biochemistry 49 6206-6218 (2010)
  10. Integrating constitutive gene expression and chemoactivity: mining the NCI60 anticancer screen. Covell DG. PLoS ONE 7 e44631 (2012)
  11. Radical mechanism of cyanophage phycoerythrobilin synthase (PebS). Busch AW, Reijerse EJ, Lubitz W, Hofmann E, Frankenberg-Dinkel N. Biochem. J. 433 469-476 (2011)
  12. How to produce a chemical defense: structural elucidation and anatomical distribution of aplysioviolin and phycoerythrobilin in the sea hare Aplysia californica. Kamio M, Nguyen L, Yaldiz S, Derby CD. Chem. Biodivers. 7 1183-1197 (2010)
  13. Insights into the biosynthesis and assembly of cryptophycean phycobiliproteins. Overkamp KE, Gasper R, Kock K, Herrmann C, Hofmann E, Frankenberg-Dinkel N. J. Biol. Chem. 289 26691-26707 (2014)
  14. New biosynthetic pathway for pink pigments from uncultured oceanic viruses. Ledermann B, Béjà O, Frankenberg-Dinkel N. Environ. Microbiol. 18 4337-4347 (2016)
  15. Letter Atomic-resolution structure of the phycocyanobilin:ferredoxin oxidoreductase I86D mutant in complex with fully protonated biliverdin. Hagiwara Y, Wada K, Irikawa T, Sato H, Unno M, Yamamoto K, Fukuyama K, Sugishima M. FEBS Lett. 590 3425-3434 (2016)