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Determined Crystal Structure (determine + crystal_structure)
Selected AbstractsElectron diffraction, X-ray powder diffraction and pair-distribution-function analyses to determine the crystal structures of Pigment Yellow 213, C23H21N5O9ACTA CRYSTALLOGRAPHICA SECTION B, Issue 2 2009Martin U. Schmidt The crystal structure of the nanocrystalline , phase of Pigment Yellow 213 (P.Y. 213) was solved by a combination of single-crystal electron diffraction and X-ray powder diffraction, despite the poor crystallinity of the material. The molecules form an efficient dense packing, which explains the observed insolubility and weather fastness of the pigment. The pair-distribution function (PDF) of the , phase is consistent with the determined crystal structure. The , phase of P.Y. 213 shows even lower crystal quality, so extracting any structural information directly from the diffraction data is not possible. PDF analysis indicates the , phase to have a columnar structure with a similar local structure as the , phase and a domain size in column direction of approximately 4,nm. [source] The structural plasticity of Tom71 for mitochondrial precursor translocationsACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2010Jingzhi Li Mitochondrial precursors are transported through the translocase of the outer membrane (TOM) complex. Tom70/Tom71 is a major surface receptor of the TOM complex for mitochondrial precursors and facilitates Hsp70/Hsp90-escorted precursor translocation into the mitochondrion. Previous structural studies of Tom71 have revealed that it contains an N-terminal and a C-terminal domain and that the two domains may remain in an open conformation when binding to Hsp70/Hsp90. In a newly obtained crystal form of a complex of Tom71 and the Hsp70 C-terminus, the N-terminal domain was found to have rotated about 12° towards the C-terminal domain compared with the previous determined crystal structure of Tom71 in the open conformation. This newly solved structure is defined as the `intermediate conformation'. The domain rearrangements in Tom71 significantly change the surface hydrophobicity and the volume of the precursor-binding pocket. This work suggests that Tom70/Tom71-family members may exhibit structural plasticity from the intermediate conformation to the fully open conformation when complexed with Hsp70/Hsp90. This structural plasticity enables the precursor receptors to accommodate different precursor substrates for mitochondrial translocation. [source] The structure of PhaZ7 at atomic (1.2,Å) resolution reveals details of the active site and suggests a substrate-binding modeACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2010Sachin Wakadkar Poly-(R)-hydroxyalkanoates (PHAs) are bacterial polyesters that are degraded by a group of enzymes known as PHA depolymerases. Paucimonas lemoignei PhaZ7 depolymerase is the only extracellular depolymerase that has been described as being active towards amorphous PHAs. A previously determined crystal structure of PhaZ7 revealed an ,/,-hydrolase fold and a Ser-His-Asp catalytic triad. In order to address questions regarding the catalytic mechanism and substrate binding, the atomic resolution structure of PhaZ7 was determined after cocrystallization with the protease inhibitor PMSF. The reported structure has the highest resolution (1.2,Å) of currently known depolymerase structures and shows a sulfur dioxide molecule covalently attached to the active-site residue Ser136. Structural comparison with the free PhaZ7 structure (1.45,Å resolution) revealed no major changes in the active site, suggesting a preformed catalytic triad. The oxyanion hole was found to be formed by the amide groups of Met137 and Asn49. Nine well ordered water molecules were located in the active site. Manual docking of a substrate trimer showed that the positions of these water molecules coincide well with the substrate atoms. It is proposed that these water molecules are displaced upon binding of the substrate. Furthermore, conformational changes were identified after comparison with a previously determined PhaZ7 dimer structure in a different space group. The changes were located in surface loops involved in dimer formation, indicating some flexibility of these loops and their possible involvement in polyester binding. [source] Structural basis for the binding of naproxen to human serum albumin in the presence of fatty acids and the GA moduleACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2008Sara Lejon The previously determined crystal structure of the bacterial albumin-binding GA module in complex with human serum albumin (HSA) suggested the possibility of utilizing the complex in the study of ligand binding to HSA. As a continuation of these studies, the crystal structure of the HSA,GA complex with the drug molecule naproxen and the fatty acid decanoate bound to HSA has been determined to a resolution of 2.5,Å. In terms of drug binding, the structure suggests that the binding of decanoate to the albumin molecule may play a role in making the haemin site in subdomain IB of the albumin molecule available for the binding of naproxen. In addition, structure comparisons with solved structures of HSA and of the HSA,GA complex show that the GA module is capable of binding to different conformations of HSA. The HSA,GA complex therefore emerges as a possible platform for the crystallographic study of specific HSA,drug interactions and of the influence exerted by the presence of fatty acids. [source] Unexpected Novel Binding Mode of Pyrrolidine-Based Aspartyl Protease Inhibitors: Design, Synthesis and Crystal Structure in Complex with HIV ProteaseCHEMMEDCHEM, Issue 1 2006Edgar Specker Dr. Abstract At present nine FDA-approved HIV protease inhibitors have been launched to market, however rapid drug resistance arising under antiviral therapy calls upon novel concepts. Possible strategies are the development of ligands with less peptide-like character or the stabilization of a new and unexpected binding-competent conformation of the protein through a novel ligand-binding mode. Our rational design of pyrrolidinedimethylene diamines was inspired by the idea to incorporate key structural elements from classical peptidomimetics with a non-peptidic heterocyclic core comprising an endocyclic amino function to address the catalytic aspartic acid side chains of Asp,25 and 25,. The basic scaffolds were decorated by side chains already optimized for the recognition pockets of HIV protease or cathepsin,D. A multistep synthesis has been established to produce the central heterocycle and to give flexible access to side chain decorations. Depending on the substitution pattern of the pyrrolidine moiety, single-digit micromolar inhibition of HIV-1 protease and cathepsin,D has been achieved. Successful design is suggested in agreement with our modelling concepts. The subsequently determined crystal structure with HIV protease shows that the pyrrolidine moiety binds as expected to the pivotal position between both aspartic acid side chains. However, even though the inhibitors have been equipped symmetrically by polar acceptor groups to address the flap water molecule, it is repelled from the complex, and only one direct hydrogen bond is formed to the flap. A strong distortion of the flap region is detected, leading to a novel hydrogen bond which cross-links the flap loops. Furthermore, the inhibitor addresses only three of the four available recognition pockets. It achieves only an incomplete desolvation compared with the similarly decorated amprenavir. Taking these considerations into account it is surprising that the produced pyrrolidine derivatives achieve micromolar inhibition and it suggests extraordinary potency of the new compound class. Most likely, the protonated pyrrolidine moiety experiences strong enthalpic interactions with the enzyme through the formation of two salt bridges to the aspartic acid side chains. This might provide challenging opportunities to combat resistance of the rapidly mutating virus. 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