Document Detail

Potential transition-state analogs for glycosyltransferases. Design and DFT calculations of conformational behavior.
MedLine Citation:
PMID:  15780269     Owner:  NLM     Status:  MEDLINE    
The structure of a previously calculated transition state (TS) was used to design the [tetrahydro-2-(methylthio)furan-2-yl]methyl phosphate dianion (1) as a new scaffold for transition-state analogs of reactions catalyzed by the inverting glycosyltransferases. This scaffold contains relevant features of the donor and acceptor and represents a new type of potential inhibitors for these enzymes. Available conformational space of 1 was explored using DFT quantum chemical methods by means of two-dimensional potential-energy maps calculated as a function of Phi, Psi, and omega dihedral angles at the B3LYP/6-31+G* level. The calculated potential energy surfaces revealed the existence of several low-energy domains. Structures from these regions were refined at the 6-311++G** level and led to 14 conformers. The stability of conformers is influenced by their environment, and in aqueous solution two conformers dominate the equilibrium. A superposition of calculated conformers with the predicted TS structure revealed that the preferred conformers in solution nicely mimic structural features of the TS. These results imply that 1 has structural properties required to mimic the TS and therefore can be used as a scaffold for further development of TS-analog inhibitors for retaining glycosyltransferases.
Michal Raab; Stanislav Kozmon; Igor Tvaroska
Related Documents :
14530289 - Inhibition of fructose-1,6-bisphosphatase by a new class of allosteric effectors.
21060909 - Correlating allostery with rigidity.
15261589 - Molecular dynamics (md) simulations for the prediction of chiral discrimination of n-ac...
21697089 - Structural and functional evolution of isopropylmalate dehydrogenases in the leucine an...
16981689 - X-ray, nmr, and mutational studies of the catalytic cycle of the gdp-mannose mannosyl h...
22056329 - Structure of the glycosyltransferase eryciii in complex with its activating p450 homolo...
14587279 - Papain-like lysosomal cysteine proteases and their inhibitors: drug discovery targets?
8102879 - Hydrolysis of adenosine 5'-triphosphate by escherichia coli groel: effects of groes and...
15923229 - Signaling through receptors and scaffolds: independent interactions reduce combinatoria...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Carbohydrate research     Volume:  340     ISSN:  0008-6215     ISO Abbreviation:  Carbohydr. Res.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-22     Completed Date:  2005-11-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0043535     Medline TA:  Carbohydr Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1051-7     Citation Subset:  IM    
Institute of Chemistry, Slovak Academy of Sciences, Dúbravska cesta 9, 845 38 Bratislava, Slovakia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Computer Simulation
Furans / chemistry*
Glycosyltransferases / metabolism*
Molecular Conformation
Phosphoric Acid Esters / chemistry*
Reg. No./Substance:
0/(tetrahydro-2-(methylthio)furan-2-yl)methyl phosphate; 0/Furans; 0/Phosphoric Acid Esters; EC 2.4.-/Glycosyltransferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  A dynamic perspective on the molecular recognition of chitooligosaccharide ligands by hevein domains...
Next Document:  The use of a genetic algorithm search for molecular mechanics (MM3)-based conformational analysis of...