3tuv

Crystal structure of insulysin with bound ATP

spinqualitylabelsall models 3tuv, resolution 2.27Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3tuv is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP NonStd Res: UNK Gene: Ide (Buffalo rat) Activity: Insulysin, with EC number 3.4.24.56 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IDE_RAT] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. Publication Abstract from PubMed Insulin-degrading enzyme (IDE) (insulysin) is a zinc metallopeptidase that metabolizes several bioactive peptides, including insulin and the amyloid beta peptide. IDE is an unusual metallopeptidase in that it is allosterically activated by both small peptides and anions, such as ATP. Here, we report that the ATP-binding site is located on a portion of the substrate binding chamber wall arising largely from domain 4 of the four-domain IDE. Two variants having residues in this site mutated, IDE(K898A,K899A,S901A) and IDE(R429S), both show greatly decreased activation by the polyphosphate anions ATP and PPP(i). IDE(K898A,K899A,S901A) is also deficient in activation by small peptides, suggesting a possible mechanistic link between the two types of allosteric activation. Sodium chloride at high concentrations can also activate IDE. There are no observable differences in average conformation between the IDE-ATP complex and unliganded IDE, but regions of the active site and C-terminal domain do show increased crystallographic thermal factors in the complex, suggesting an effect on dynamics. Activation by ATP is shown to be independent of the ATP hydrolysis activity reported for the enzyme. We also report that IDE(K898A,K899A,S901A) has reduced intracellular function relative to unmodified IDE, consistent with a possible role for anion activation of IDE activity in vivo. Together, the data suggest a model in which the binding of anions activates by reducing the electrostatic attraction between the two halves of the enzyme, shifting the partitioning between open and closed conformations of IDE toward the open form. Anion Activation Site of Insulin-degrading Enzyme.,Noinaj N, Song ES, Bhasin S, Alper BJ, Schmidt WK, Hersh LB, Rodgers DW J Biol Chem. 2012 Jan 2;287(1):48-57. Epub 2011 Nov 2. PMID:22049080 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Insulin-degrading enzyme 3D structures RNA polymerase 3D structures

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