The structures of enzymes catalyzing the reactions in central metabolic pathways are generally well conserved as are their catalytic mechanisms. The two types of 3-dehydroquinate dehydratase (DHQase) are therefore most unusual since they are unrelated at the sequence level and they utilize completely different mechanisms to catalyze the same overall reaction. The type I enzymes catalyze a cis-dehydration of 3-dehydroquinate via a covalent imine intermediate, while the type II enzymes catalyze a trans-dehydration via an enolate intermediate. Here we report the three-dimensional structures of a representative member of each type of biosynthetic DHQase. Both enzymes function as part of the shikimate pathway, which is essential in microorganisms and plants for the biosynthesis of aromatic compounds including folate, ubiquinone and the aromatic amino acids. An explanation for the presence of two different enzymes catalyzing the same reaction is presented. The absence of the shikimate pathway in animals makes it an attractive target for antimicrobial agents. The availability of these two structures opens the way for the design of highly specific enzyme inhibitors with potential importance as selective therapeutic agents.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/9287 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ruthenium-Catalyzed Intramolecular Allene-alkyne Cascade Cyclization: Access to the Sulfone-cyclopenta[]naphthalene Core.
Org Lett
January 2025
Department of Chemistry, Indian Institute of Technology Ropar, Rupnagar, Punjab 140001, India.
A ruthenium-catalyzed intramolecular cascade cyclization of allene-alkyne has been achieved. This method offers a streamlined and atom-economical approach for the construction of sulfone bearing 1-cyclopenta[]naphthalenes, an important structural scaffold that exists in biologically active compounds. Our approach, backed by mechanistic insights from deuterium labeling, DFT calculations, and potential for reaction scale-up, presents synthetic chemists with an invaluable tool for efficiently producing a distinct carbon framework in a one-pot manner.
View Article and Find Full Text PDFRhodium-Catalyzed Homogeneous Asymmetric Hydrogenation of Naphthol Derivatives.
J Am Chem Soc
January 2025
National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China.
Due to their strong aromaticity and difficulties in chemo-, regio-, and enantioselectivity control, asymmetric hydrogenation of naphthol derivatives to 1,2,3,4-tetrahydronaphthols has remained a long-standing challenge. Herein, we report the first example of homogeneous asymmetric hydrogenation of naphthol derivatives catalyzed by tethered rhodium-diamine catalysts, affording a wide array of optically pure 1,2,3,4-tetrahydronaphthols in high yields with excellent regio-, chemo-, and enantioselectivities (up to 98% yield and >99% ee). Mechanistic studies with experimental and computational approaches reveal that fluorinated solvent 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) plays vital roles in the control of reactivity and selectivity, and 1-naphthol is reduced via a cascade reaction pathway, including dearomative tautomerization, 1,4-hydride addition, and 1,2-hydride addition in sequence.
View Article and Find Full Text PDFCopper(II)-Catalyzed Asymmetric (3+3) Annulation of Diaziridines with Oxiranes.
Org Lett
January 2025
State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, China.
Highly asymmetric (3+3) annulation of diaziridines with oxiranes via C-N bond cleavage in diaziridine was achieved under 10 mol % of chiral copper(II) complex as the catalyst under mild reaction conditions. With Cu(OTf) as the Lewis acid and C-symmetric imidazolidine-pyrroloimidazolone pyridine as the ligand, diverse tetrahydro-[1,3,4]-oxadiazines were obtained by stereospecific C-N/C-O bond formation in moderate to good yields (up to 93% yield) and high diastereo- (>20:1 dr) and enantioselectivities (up to 92% ee). The catalytic cycle and stereochemical model were proposed by DFT calculation.
View Article and Find Full Text PDFThe common chemical logic of 'bridged' peroxo species in mononuclear non-heme iron systems.
Crit Rev Biochem Mol Biol
January 2025
Department of Chemistry, Emory University, Atlanta, GA, USA.
Mononuclear non-heme iron enzymes catalyze a wide array of important oxidative transformations. They are correspondingly diverse in both structure and mechanism. Despite significant evolutionary distance, it is becoming increasingly apparent that these enzymes nonetheless illustrate a compelling case of mechanistic convergence the formation of peroxo species bridging metal and substrate.
View Article and Find Full Text PDFFunctionalization of Indoles with 1,3,5-Triazinanes: Chemistry of Aminomethylation vs the Hofmann-Martius-Type Rearrangement.
J Org Chem
January 2025
Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram 695019, India.
We have developed efficacious routes toward the selective synthesis of two classes of compounds such as C-3 amino-methylated indoles and 4-indol-3-yl-methylanilines from the same precursors, namely, indoles and 1,3,5-triazinanes. It is reported that the controlled cleavage of 1,3,5-triazinanes can be effected by heat for the generation of aryl imine motifs, and we observed that the presence of Lewis acid influences the course of these transformations toward different products. The reaction toward indol-3-yl-methylanilines proceeds via a nucleophilic attack of indole to the aryl imine generated from the 1,3,5-triazinanes to form an amino-methylated product which undergoes a Lewis acid mediated Hofmann-Martius-type rearrangement.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!