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The crystal structure of cystathionine gamma-synthase from Nicotiana tabacum reveals its substrate and reaction specificity.

Steegborn C, Messerschmidt A, Laber B, Streber W, Huber R, Clausen T
J Mol Biol 290 983-96 (1999)
Cited: 20 times
EuropePMC logo PMID: 10438597

Abstract

Cystathionine gamma-synthase catalyses the committed step of de novo methionine biosynthesis in micro-organisms and plants, making the enzyme an attractive target for the design of new antibiotics and herbicides. The crystal structure of cystathionine gamma-synthase from Nicotiana tabacum has been solved by Patterson search techniques using the structure of Escherichia coli cystathionine gamma-synthase. The model was refined at 2.9 A resolution to a crystallographic R -factor of 20.1 % (Rfree25.0 %). The physiological substrates of the enzyme, L-homoserine phosphate and L-cysteine, were modelled into the unliganded structure. These complexes support the proposed ping-pong mechanism for catalysis and illustrate the dissimilar substrate specificities of bacterial and plant cystathionine gamma-synthases on a molecular level. The main difference arises from the binding modes of the distal substrate groups (O -acetyl/succinyl versusO -phosphate). Central in fixing the distal phosphate of the plant CGS substrate is an exposed lysine residue that is strictly conserved in plant cystathionine gamma-synthases whereas bacterial enzymes carry a glycine residue at this position. General insight regarding the reaction specificity of transsulphuration enzymes is gained by the comparison to cystathionine beta-lyase from E. coli, indicating the mechanistic importance of a second substrate binding site for L-cysteine which leads to different chemical reaction types.

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  2. H2r: identification of evolutionary important residues by means of an entropy based analysis of multiple sequence alignments. Merkl R, Zwick M. BMC Bioinformatics 9 151 (2008)
  3. New methods to measure residues coevolution in proteins. Gao H, Dou Y, Yang J, Wang J. BMC Bioinformatics 12 206 (2011)
  4. Discovery and characterization of small molecule inhibitors of cystathionine gamma-synthase with in planta activity. Bloch I, Haviv H, Rapoport I, Cohen E, Shushan RSB, Dotan N, Sher I, Hacham Y, Amir R, Gal M. Plant Biotechnol J 19 1785-1797 (2021)
  5. Expression, crystallization and preliminary X-ray crystallographic analysis of cystathionine β-lyase from Acinetobacter baumannii OXA-23. Nguyen DQ, Ngo HP, Ahn YJ, Lee SH, Kang LW. Acta Crystallogr F Struct Biol Commun 70 1368-1371 (2014)
  6. Expression, purification and preliminary crystallographic analysis of O-acetylhomoserine sulfhydrylase from Mycobacterium tuberculosis. Yin J, Garen CR, Bateman K, Yu M, Lyon EZ, Habel J, Kim H, Hung LW, Kim CY, James MN. Acta Crystallogr Sect F Struct Biol Cryst Commun 67 959-963 (2011)
  7. The hyperthermophilic cystathionine γ-synthase from the aerobic crenarchaeon Sulfolobus tokodaii: expression, purification, crystallization and structural insights. Sato D, Shiba T, Mizuno S, Kawamura A, Hanada S, Yamada T, Shinozaki M, Yanagitani M, Tamura T, Inagaki K, Harada S. Acta Crystallogr F Struct Biol Commun 73 152-158 (2017)


Reviews citing this publication (2)

  1. Synthesis of the sulfur amino acids: cysteine and methionine. Wirtz M, Droux M. Photosynth Res 86 345-362 (2005)
  2. Recent progress in deciphering the biosynthesis of aspartate-derived amino acids in plants. Jander G, Joshi V. Mol Plant 3 54-65 (2010)

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  2. Gene clusters for insecticidal loline alkaloids in the grass-endophytic fungus Neotyphodium uncinatum. Spiering MJ, Moon CD, Wilkinson HH, Schardl CL. Genetics 169 1403-1414 (2005)
  3. Determinants of enzymatic specificity in the Cys-Met-metabolism PLP-dependent enzymes family: crystal structure of cystathionine gamma-lyase from yeast and intrafamiliar structure comparison. Messerschmidt A, Worbs M, Steegborn C, Wahl MC, Huber R, Laber B, Clausen T. Biol Chem 384 373-386 (2003)
  4. Aspartate-Derived Amino Acid Biosynthesis in Arabidopsis thaliana. Jander G, Joshi V. Arabidopsis Book 7 e0121 (2009)
  5. Regulation of one-carbon metabolism in Arabidopsis: the N-terminal regulatory domain of cystathionine gamma-synthase is cleaved in response to folate starvation. Loizeau K, Gambonnet B, Zhang GF, Curien G, Jabrin S, Van Der Straeten D, Lambert WE, Rébeillé F, Ravanel S. Plant Physiol 145 491-503 (2007)
  6. The three-dimensional structure of cystathionine beta-lyase from Arabidopsis and its substrate specificity. Breitinger U, Clausen T, Ehlert S, Huber R, Laber B, Schmidt F, Pohl E, Messerschmidt A. Plant Physiol 126 631-642 (2001)
  7. Purification and characterization of the aromatic desulfinase, 2-(2'-hydroxyphenyl)benzenesulfinate desulfinase. Watkins LM, Rodriguez R, Schneider D, Broderick R, Cruz M, Chambers R, Ruckman E, Cody M, Mrachko GT. Arch Biochem Biophys 415 14-23 (2003)
  8. Crystal structures of cystathionine gamma-synthase inhibitor complexes rationalize the increased affinity of a novel inhibitor. Steegborn C, Laber B, Messerschmidt A, Huber R, Clausen T. J Mol Biol 311 789-801 (2001)
  9. Identification and characterization of a methionine γ-lyase in the calicheamicin biosynthetic cluster of Micromonospora echinospora. Song H, Xu R, Guo Z. Chembiochem 16 100-109 (2015)
  10. Exploration of the active site of Escherichia coli cystathionine γ-synthase. Jaworski AF, Lodha PH, Manders AL, Aitken SM. Protein Sci 21 1662-1671 (2012)
  11. A role for glutamate-333 of Saccharomyces cerevisiae cystathionine γ-lyase as a determinant of specificity. Hopwood EM, Ahmed D, Aitken SM. Biochim Biophys Acta 1844 465-472 (2014)


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