Structural features of the aldose reductase and aldehyde reductase inhibitor-binding sites. 1998

O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia. ossama.el-kabbani@vcp.monash.edu.au

The three-dimensional structures of aldose reductase and aldehyde reductase, members of the aldo-keto reductase superfamily, are composed of similar alpha/beta TIM-barrels. However, examination of the structures reveals that the inhibitor-binding site of aldose reductase differs from that of aldehyde reductase due to the participation of non-conserved residues in its formation. This information will be useful in the design of inhibitors to prevent or delay diabetic retinopathy. A review of the structures of the inhibitor-binding sites is presented.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D003929 Diabetic Neuropathies Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325) Diabetic Amyotrophy,Diabetic Autonomic Neuropathy,Diabetic Neuralgia,Diabetic Polyneuropathy,Neuralgia, Diabetic,Asymmetric Diabetic Proximal Motor Neuropathy,Diabetic Asymmetric Polyneuropathy,Diabetic Mononeuropathy,Diabetic Mononeuropathy Simplex,Diabetic Neuropathy, Painful,Mononeuropathy, Diabetic,Symmetric Diabetic Proximal Motor Neuropathy,Amyotrophies, Diabetic,Amyotrophy, Diabetic,Asymmetric Polyneuropathies, Diabetic,Asymmetric Polyneuropathy, Diabetic,Autonomic Neuropathies, Diabetic,Autonomic Neuropathy, Diabetic,Diabetic Amyotrophies,Diabetic Asymmetric Polyneuropathies,Diabetic Autonomic Neuropathies,Diabetic Mononeuropathies,Diabetic Mononeuropathy Simplices,Diabetic Neuralgias,Diabetic Neuropathies, Painful,Diabetic Neuropathy,Diabetic Polyneuropathies,Mononeuropathies, Diabetic,Mononeuropathy Simplex, Diabetic,Mononeuropathy Simplices, Diabetic,Neuralgias, Diabetic,Neuropathies, Diabetic,Neuropathies, Diabetic Autonomic,Neuropathies, Painful Diabetic,Neuropathy, Diabetic,Neuropathy, Diabetic Autonomic,Neuropathy, Painful Diabetic,Painful Diabetic Neuropathies,Painful Diabetic Neuropathy,Polyneuropathies, Diabetic,Polyneuropathies, Diabetic Asymmetric,Polyneuropathy, Diabetic,Polyneuropathy, Diabetic Asymmetric,Simplex, Diabetic Mononeuropathy,Simplices, Diabetic Mononeuropathy
D003930 Diabetic Retinopathy Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION. Diabetic Retinopathies,Retinopathies, Diabetic,Retinopathy, Diabetic
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000449 Aldehyde Reductase An enzyme that catalyzes reversibly the oxidation of an aldose to an alditol. It possesses broad specificity for many aldoses. EC 1.1.1.21. Aldose Reductase,Aldose Reductase Ia,Aldose Reductase Ib,Erythrose Reductase,Xylose Reductase,Reductase Ia, Aldose,Reductase Ib, Aldose,Reductase, Aldehyde,Reductase, Aldose,Reductase, Erythrose,Reductase, Xylose
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D017434 Protein Structure, Tertiary The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures

Related Publications

O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
August 2007, Cellular and molecular life sciences : CMLS,
O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
June 2008, Journal of molecular biology,
O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
January 1987, Progress in clinical and biological research,
O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
September 1999, Molecular vision,
O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
February 2009, Bioorganic & medicinal chemistry,
O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
January 1999, Biochemistry,
O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
January 1989, Progress in clinical and biological research,
O El-Kabbani, and D K Wilson, and M Petrash, and F A Quiocho
March 1983, European journal of biochemistry,
Copied contents to your clipboard!