6rfu | pdb_00006rfu

In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of ATP and GMP as genuine co-factors

spinqualitylabelsall models 6rfu, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6rfu is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5GP, ATP Activity: IMP dehydrogenase, with EC number 1.1.1.205 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IMDH_TRYBB] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Publication Abstract from PubMed Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5'-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 A resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds. In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors.,Nass K, Redecke L, Perbandt M, Yefanov O, Klinge M, Koopmann R, Stellato F, Gabdulkhakov A, Schonherr R, Rehders D, Lahey-Rudolph JM, Aquila A, Barty A, Basu S, Doak RB, Duden R, Frank M, Fromme R, Kassemeyer S, Katona G, Kirian R, Liu H, Majoul I, Martin-Garcia JM, Messerschmidt M, Shoeman RL, Weierstall U, Westenhoff S, White TA, Williams GJ, Yoon CH, Zatsepin N, Fromme P, Duszenko M, Chapman HN, Betzel C Nat Commun. 2020 Jan 30;11(1):620. doi: 10.1038/s41467-020-14484-w. PMID:32001697 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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