3zj6

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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Two similar enzymes with different biosynthetic function in one species have evolved to catalyze two distinct reactions. X-ray structures of both enzymes help reveal their most important differences. The Rauvolfia alkaloid biosynthetic network harbors two O-glucosidases: raucaffricine glucosidase (RG), which hydrolyses raucaffricine to an intermediate downstream in the ajmaline pathway, and strictosidine glucosidase (SG), which operates upstream. RG converts strictosidine, the substrate of SG, but SG does not accept raucaffricine. Now elucidation of crystal structures of RG, inactive RG-E186Q mutant, and its complexes with ligands dihydro-raucaffricine and secologanin reveals that it is the "wider gate" of RG that allows strictosidine to enter the catalytic site, whereas the "slot-like" entrance of SG prohibits access by raucaffricine. Trp392 in RG and Trp388 in SG control the gate shape and acceptance of substrates. Ser390 directs the conformation of Trp392. 3D structures, supported by site-directed mutations and kinetic data of RG and SG, provide a structural and catalytic explanation of substrate specificity and deeper insights into O-glucosidase chemistry.
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Abstract Insight into the structure and inhibition mechanism of O-beta-d-glucosidases by deoxa-pyranosylamine type inhibitors is provided by X-ray analysis of complexes between raucaffricine and strictosidine glucosidases and N-(cyclohexylmethyl)-, N-(cyclohexyl)- and N-(bromobenzyl)-beta-d-gluco-1,5-deoxa-pyranosylamine. All inhibitors anchored exclusively in the catalytic active site by competition with appropriate enzyme substrates. Thus facilitated prospective elucidation of the binding networks with residues located at &lt;3.9 A distance will enable the development of potent inhibitors suitable for the production of valuable alkaloid glucosides, raucaffricine and strictosidine, by means of synthesis in Rauvolfia serpentina cell suspension cultures.
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Structures of Alkaloid Biosynthetic Glucosidases Decode Substrate Specificity.,Xia L, Ruppert M, Wang M, Panjikar S, Lin H, Rajendran C, Barleben L, Stockigt J ACS Chem Biol. 2011 Oct 28. PMID:22004291<ref>PMID:22004291</ref>
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Ligand structures of synthetic deoxa-pyranosylamines with raucaffricine and strictosidine glucosidases provide structural insights into their binding and inhibitory behaviours.,Xia L, Lin H, Staniek A, Panjikar S, Ruppert M, Hilgers P, Williardt J, Rajendran C, Wang M, Warzecha H, Jager V, Stockigt J J Enzyme Inhib Med Chem. 2014 Aug 20:1-7. PMID:25140865<ref>PMID:25140865</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 10:35, 7 February 2015

Crystal of Raucaffricine Glucosidase in complex with inhibitor

3zj6, resolution 2.40Å

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