UNIVERSI
TÄ
TS-
BIBLIOTHEK
P
ADERBORN
Anmelden
Menü
Menü
Start
Hilfe
Blog
Weitere Dienste
Neuerwerbungslisten
Fachsystematik Bücher
Erwerbungsvorschlag
Bestellung aus dem Magazin
Fernleihe
Einstellungen
Sprache
Deutsch
Deutsch
Englisch
Farbschema
Hell
Dunkel
Automatisch
Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist
gegebenenfalls
nur via VPN oder Shibboleth (DFN-AAI) möglich.
mehr Informationen...
Universitätsbibliothek
Katalog
Suche
Details
Zur Ergebnisliste
Ergebnis 5 von 105
Datensatz exportieren als...
BibTeX
Structure of human aldose reductase holoenzyme in complex with Statil: An approach to structure-based inhibitor design of the enzyme
Proteins, structure, function, and bioinformatics, 2003-02, Vol.50 (2), p.230-238
El-Kabbani, Ossama
Ramsland, Paul
Darmanin, Connie
Chung, Roland P.-T.
Podjarny, Alberto
2003
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
El-Kabbani, Ossama
Ramsland, Paul
Darmanin, Connie
Chung, Roland P.-T.
Podjarny, Alberto
Titel
Structure of human aldose reductase holoenzyme in complex with Statil: An approach to structure-based inhibitor design of the enzyme
Ist Teil von
Proteins, structure, function, and bioinformatics, 2003-02, Vol.50 (2), p.230-238
Ort / Verlag
New York: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2003
Quelle
Wiley Online Library - AutoHoldings Journals
Beschreibungen/Notizen
Aldose reductase, a monomeric NADPH‐dependent oxidoreductase, catalyzes the reduction of a wide variety of aldehydes and ketones to their corresponding alcohols. The X‐ray structure of human aldose reductase holoenzyme in complex with statil was determined at a resolution of 2.1 Å. The carboxylate group of statil interacted with the conserved anion binding site located between the nicotinamide ring of the coenzyme and active site residues Tyr48, His110, and Trp111. Statil's hydrophobic phthalazinyl ring was bound in an adjacent pocket lined by residues Trp20, Phe122, and Trp219, with the bromo‐fluorobenzyl group penetrating the “specificity” pocket. The interactions between the inhibitor's bromo‐fluorobenzyl group and the enzyme include the stacking against the side‐chain of Trp111 as well as hydrogen bonding to residues Leu300 and Thr113. Based on the model of the ternary complex, the program GRID was used in an attempt to design novel potential inhibitors of human aldose reductase with enhanced binding energies of the complex. Molecular modeling calculations suggested that the replacement of the fluorine atom of statil with a carboxylate functional group may enhance the binding energies of the complex by 33%. Proteins 2003;50:230–238. © 2002 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0887-3585, 1097-0134
eISSN: 1097-0134
DOI: 10.1002/prot.10278
Titel-ID: cdi_hal_primary_oai_HAL_hal_04143731v1
Format
–
Schlagworte
Aldehyde Reductase - antagonists & inhibitors
,
Aldehyde Reductase - chemistry
,
Aldehyde Reductase - metabolism
,
aldose reductase inhibition
,
Binding Sites
,
Biochemistry, Molecular Biology
,
Crystallography, X-Ray
,
Drug Design
,
Enzyme Inhibitors - chemistry
,
Enzyme Inhibitors - metabolism
,
Holoenzymes - chemistry
,
Holoenzymes - metabolism
,
Humans
,
Hydrogen Bonding
,
Life Sciences
,
Models, Molecular
,
molecular modeling
,
Phthalazines - chemistry
,
Phthalazines - metabolism
,
Protein Binding
,
Protein Conformation
,
ternary complex
,
X-ray crystallography
Weiterführende Literatur
Empfehlungen zum selben Thema automatisch vorgeschlagen von
bX