The crystal structures of dihydropyrimidinases reaffirm the close relationship between cyclic amidohydrolases and explain their substrate specificity.

The Journal of Biological Chemistry
Bernhard LohkampDoreen Dobritzsch

Abstract

In eukaryotes, dihydropyrimidinase catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Here we describe the three-dimensional structures of dihydropyrimidinase from two eukaryotes, the yeast Saccharomyces kluyveri and the slime mold Dictyostelium discoideum, determined and refined to 2.4 and 2.05 angstroms, respectively. Both enzymes have a (beta/alpha)8-barrel structural core embedding the catalytic di-zinc center, which is accompanied by a smaller beta-sandwich domain. Despite loop-forming insertions in the sequence of the yeast enzyme, the overall structures and architectures of the active sites of the dihydropyrimidinases are strikingly similar to each other, as well as to those of hydantoinases, dihydroorotases, and other members of the amidohydrolase superfamily of enzymes. However, formation of the physiologically relevant tetramer shows subtle but nonetheless significant differences. The extension of one of the sheets of the beta-sandwich domain across a subunit-subunit interface in yeast dihydropyrimidinase underlines its closer evolutionary relationship to hydantoinases, whereas the slime mold enzyme shows higher similarity to the noncatalyti...Continue Reading

References

Sep 15, 1975·FEBS Letters·F CecereF Morisi
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
May 1, 1989·European Journal of Biochemistry·J Kautz, K D Schnackerz
Nov 1, 1981·Journal of Neurochemistry·M Sandberg, I Jacobson
Jan 1, 1980·Pharmacology & Therapeutics·C Wasternack
Jan 15, 1994·European Journal of Biochemistry·M KikugawaN Tamaki
Jan 1, 1996·Progress in Nucleic Acid Research and Molecular Biology·T W Traut, M E Jones
May 19, 1997·Biochemical and Biophysical Research Communications·R Sharma, R M Vohra
Jul 1, 1997·Journal of Inherited Metabolic Disease·A H van GennipA B van Kuilenburg
Apr 1, 1997·Journal of Molecular Graphics & Modelling·R M Esnouf
Feb 25, 1998·Biochemical and Biophysical Research Communications·G J Kim, H S Kim
Jul 4, 1998·European Journal of Biochemistry·T BykA Sobel
May 1, 1999·Applied Microbiology and Biotechnology·C SyldatkM Siemann
Jun 20, 2000·Biochemistry·H Shim, F M Raushel
Feb 19, 2002·Current Opinion in Biotechnology·J AltenbuchnerC Syldatk
Jun 25, 2002·Journal of Molecular Biology·Jan AbendrothDietmar Schomburg
Jul 2, 2003·Acta Crystallographica. Section D, Biological Crystallography·Elizabeth PottertonEleanor Dodson
Dec 20, 2003·The EMBO Journal·Rahul C DeoStephen M Strittmatter
Jun 16, 2004·FEBS Letters·Elke ZameitatMonika Löffler
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jan 1, 1993·Acta Crystallographica. Section D, Biological Crystallography·A T Brünger
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Dec 22, 2004·Biochemistry·Tamiko N PorterFrank M Raushel
Mar 1, 2005·Journal of Molecular Biology·K V Radha KishanRakesh Sharma
Apr 27, 2005·Biochemistry·Clara M Seibert, Frank M Raushel
May 11, 2005·Biochemistry·Ricardo Martí-ArbonaFrank M Raushel
Mar 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Doreen DobritzschJure Piskur
Mar 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Bernhard LohkampDoreen Dobritzsch
Jan 1, 1997·Methods in Enzymology·E A Merritt, D J Bacon

❮ Previous
Next ❯

Citations

Aug 28, 2013·Journal of Molecular Evolution·Matthieu BarbaBernard Labedan
Dec 5, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Sergio Martínez-RodríguezJuan Manuel García-Ruíz
Nov 6, 2009·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Xueyao ZhangAihua Liang
Jan 16, 2016·International Journal of Molecular Sciences·Yoko NakajimaAndré B P Van Kuilenburg
Apr 20, 2010·Expert Opinion on Drug Metabolism & Toxicology·Ching-Chen HsuYuh-Shyong Yang
Aug 12, 2015·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Birgitte Munch-PetersenWolfgang Knecht
Jun 14, 2008·Journal of Molecular Biology·Gorm AndersenJure Piskur
Mar 27, 2007·Molecular Genetics and Metabolism·André B P van KuilenburgAnnet M Bosch
Jan 26, 2007·Journal of Neurochemistry·Pål StenmarkPetri Kursula
Feb 5, 2013·Journal of Neurochemistry·Rajesh Ponnusamy, Bernhard Lohkamp
Dec 18, 2013·Biochimie·Ana Isabel Martínez-GómezSergio Martínez-Rodríguez
Sep 23, 2008·Journal of Molecular Biology·Daniel KressLars-Oliver Essen
Apr 7, 2010·Biochimica Et Biophysica Acta·André B P van KuilenburgRaoul C M Hennekam
Oct 1, 2008·FEMS Yeast Research·Halfdan BeckJure Piskur
Sep 1, 2016·Biochemical and Biophysical Research Communications·Ching-Ting TzengCheng-Yang Huang
Jun 24, 2017·Biochemical Pharmacology·Eiji HishinumaMasahiro Hiratsuka
Apr 19, 2018·Bioinorganic Chemistry and Applications·Jen-Hao ChengCheng-Yang Huang
May 7, 2019·Frontiers in Microbiology·Mikel Iradi-SerranoUnai Ugalde

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.