5ilo

Crystal structure of photoreceptor dehydrogenase from Drosophila melanogaster

spinqualitylabelsall models 5ilo, resolution 2.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ilo is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.71Å Ligands: NAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9VV42_DROME Publication Abstract from PubMed The 11-cis-retinylidene chromophore of visual pigments isomerizes upon interaction with a photon, initiating a downstream cascade of signaling events that ultimately lead to visual perception. 11-cis-Retinylidene is regenerated through enzymatic transformations collectively called the visual cycle. The first and rate-limiting enzymatic reaction within this cycle, i.e., the reduction of all-trans-retinal to all-trans-retinol, is catalyzed by retinol dehydrogenases. Here, we determined the structure of Drosophila melanogaster photoreceptor retinol dehydrogenase (PDH) isoform C that belongs to the short-chain dehydrogenase/reductase (SDR) family. This is the first reported structure of a SDR that possesses this biologically important activity. Two crystal structures of the same enzyme grown under different conditions revealed a novel conformational change of the NAD(+) cofactor, likely representing a change during catalysis. Amide hydrogen-deuterium exchange of PDH demonstrated changes in the structure of the enzyme upon dinucleotide binding. In D. melanogaster, loss of PDH activity leads to photoreceptor degeneration that can be partially rescued by transgenic expression of human RDH12. Based on the structure of PDH, we analyzed mutations causing Leber congenital amaurosis 13 in a homology model of human RDH12 to obtain insights into the molecular basis of RDH12 disease-causing mutations. Structural Insights into the Drosophila melanogaster Retinol Dehydrogenase, a Member of the Short-Chain Dehydrogenase/Reductase Family.,Hofmann L, Tsybovsky Y, Alexander NS, Babino D, Leung NY, Montell C, Banerjee S, von Lintig J, Palczewski K Biochemistry. 2016 Nov 29;55(47):6545-6557. doi: 10.1021/acs.biochem.6b00907., Epub 2016 Nov 16. PMID:27809489 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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