Fluoreszierende Inhibitoren von IspF, einem Enzym im “Nicht‐Mevalonat‐Biosyntheseweg” der Isoprenoide und möglichen Ziel einer Antimalariatherapie

The pick of the pockets: The first inhibitors for IspD, an enzyme from the non‐mevalonate pathway of isoprenoid biosynthesis, are described. High‐throughput‐screening revealed a hit with an IC50 value of 140 nM. Co‐crystal structure analyses of the binding mode in the newly formed allosteric pocket (see structure, red ball: water O atom), lead to the synthesis of a set of 17 derivatives which were tested to optimize the herbicidal activity.

show abstract

“…[7] For the subsequent enzymes of the pathway, IspD-IspH, inhibitors for IspE [8] and IspF [9] have been reported recently.…”

Section: In Memoriam Viktoriya Illarionovamentioning

confidence: 99%

Inhibitors of the Herbicidal Target IspD: Allosteric Site Binding

Witschel

Höffken²,

Seet

et al. 2011

Angew Chem Int Ed

Self Cite

View full text Add to dashboard Cite

show abstract

“…[7] Für die nachfolgenden Enzyme des Biosyntheseweges, IspD bis IspH, wurden erst vor Kurzem Inhibitoren für IspE [8] und IspF [9] beschrieben. Da IspD durch Antisense-Experimente als essenziell für Pflanzen validiert werden konnte, sollten Hemmstoffe dieses Enzyms eine herbizide Wirkung zeigen.…”

Section: In Memoriam Dr Viktoriya Illarionovaunclassified

Inhibitoren des Herbizid‐Targets IspD: Bindung in einer allosterischen Tasche

et al. 2011

Self Cite

View full text Add to dashboard Cite

In eine neue Tasche gesteckt: Die ersten Inhibitoren für IspD, ein Enzym aus dem mevalonatunabhängigen Biosyntheseweg zu Isoprenoiden, wurden erhalten. Ein Hochdurchsatz‐Screening deckte einen Inhibitor mit einem IC50‐Wert von 140 nM auf. Die Analyse der Enzym‐Ligand‐Kokristallstruktur zeigte einen allosterischen Bindungsmodus; eine Serie von 17 Analoga wurde zur Optimierung der Aktivität synthetisiert und getestet.

show abstract

“…We recently became interested in new antimalarial targets [4] and started the development of inhibitors against IspF (2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase, ybgB), one of the seven enzymes in the non-mevalonate pathway. [5] This pathway is used for isoprenoid biosynthesis by the malarial plasmodium (and other) parasites but not by humans.…”

Section: Introductionmentioning

confidence: 99%

Phosphate Recognition in Structural Biology

2006

Self Cite

View full text Add to dashboard Cite

Drug-discovery research in the past decade has seen an increased selection of targets with phosphate recognition sites, such as protein kinases and phosphatases, in the past decade. This review attempts, with the help of database-mining tools, to give an overview of the most important principles in molecular recognition of phosphate groups by enzymes. A total of 3003 X-ray crystal structures from the RCSB Protein Data Bank with bound organophosphates has been analyzed individually, in particular for H-bonding interactions between proteins and ligands. The various known binding motifs for phosphate binding are reviewed, and similarities to phosphate complexation by synthetic receptors are highlighted. An analysis of the propensities of amino acids in various classes of phosphate-binding enzymes showed characteristic distributions of amino acids used for phosphate binding. This review demonstrates that structure-based lead development and optimization should carefully address the phosphate-binding-site environment and also proposes new alternatives for filling such sites.

show abstract

Fluoreszierende Inhibitoren von IspF, einem Enzym im “Nicht‐Mevalonat‐Biosyntheseweg” der Isoprenoide und möglichen Ziel einer Antimalariatherapie

Cited by 19 publications

References 38 publications

Inhibitors of the Herbicidal Target IspD: Allosteric Site Binding

Inhibitors of the Herbicidal Target IspD: Allosteric Site Binding

Inhibitoren des Herbizid‐Targets IspD: Bindung in einer allosterischen Tasche

Phosphate Recognition in Structural Biology

Contact Info

Product

Resources

About