4bva

Crystal structure of the NADPH-T3 form of mouse Mu-crystallin.

spinqualitylabelsall models 4bva, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bva is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: K, NDP, T3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CRYM_MOUSE Specifically catalyzes the reduction of imine bonds in brain substrates that may include cystathionine ketimine (CysK) and lanthionine ketimine (LK). Binds thyroid hormone which is a strong reversible inhibitor. Presumably involved in the regulation of the free intracellular concentration of triiodothyronine and access to its nuclear receptors (By similarity). Publication Abstract from PubMed Mu-Crystallin (CRYM), first described as a structural component of the eye lens in marsupials, has been characterized as a NADPH-dependent cytosolic T3 thyroid hormone (triiodotyronine) binding protein. More recently, Mu-Crystallin has also been associated with ketimine reductase activity. Here, we report three crystal structures: mouse CRYM (mCRYM) in its apo form, in a form complexed with NADPH, and in a form with both NADPH and triiodotyronine bound. Comparison of apo and NADPH forms reveals a rearrangement of the protein upon NADPH binding that reduces the degrees of freedom of several residues and traps the conformation of the binding pocket in a more T3 competent state. These findings are in agreement with the cooperative mechanism identified using isothermal titration calorimetry. Our structure with T3 reveals for the first time the location of the hormone binding site and shows its detailed interactions. T3 binding involves mainly hydrophobic interactions. Only five residues, either directly or through bridging water molecules, are hydrogen-bonded to the hormone. Using in silico docking analysis, a series of ring-containing hydrophobic molecules were identified as potential mCRYM ligands, suggesting that the specificity for the recognition of the hydrophobic part of the hormone might be low. This is in agreement with the ketimine reductase activity that has been identified for ovine CRYM, as it demonstrates how a protein known as a thyroid hormone transporter can accommodate the ringed molecules required for its ketimine reductase activity. In the light of our results, a putative role of CRYM in thyroid hormone metabolism is also discussed. This article is protected by copyright. All rights reserved. STRUCTURED DIGITAL ABSTRACT: CRYM and CRYM bind by x-ray crystallography (View interaction). Crystal Structure of mouse Mu-crystallin complexed with NADPH and the T3 thyroid hormone.,Borel F, Hachi I, Palencia A, Gaillard MC, Ferrer JL FEBS J. 2014 Jan 27. doi: 10.1111/febs.12726. PMID:24467707 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA