5luz

Structure of Human Neurolysin (E475Q) in complex with neurotensin peptide products

spinqualitylabelsall models 5luz, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5luz is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: CL, GOL, PCA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NEUL_HUMAN Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. Publication Abstract from PubMed Proteolysis plays an important role in mitochondrial biogenesis, from the processing of newly imported precursor proteins to the degradation of mitochondrial targeting peptides. Disruption of peptide degradation activity in yeast, plant and mammalian mitochondria is known to have deleterious consequences for organism physiology, highlighting the important role of mitochondrial peptidases. In the present work, we show that the human mitochondrial peptidase neurolysin (hNLN) can degrade mitochondrial presequence peptides as well as other fragments up to 19 amino acids long. The crystal structure of hNLN(E475Q) in complex with the products of neurotensin cleavage at 2.7A revealed a closed conformation with an internal cavity that restricts substrate length and highlighted the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. Analysis of peptide degradation in vitro showed that hNLN cooperates with presequence protease (PreP or PITRM1) in the degradation of long targeting peptides and amyloid-beta peptide, Abeta1-40, associated with Alzheimer disease, particularly cleaving the hydrophobic fragment Abeta35-40. These findings suggest that a network of proteases may be required for complete degradation of peptides localized in mitochondria. Mechanism of peptide binding and cleavage by the human mitochondrial peptidase neurolysin.,Teixeira PF, Masuyer G, Pinho CM, Branca RMM, Kmiec B, Wallin C, Warmlander SKTS, Berntsson RP, Ankarcrona M, Graslund A, Lehtio J, Stenmark P, Glaser E J Mol Biol. 2017 Nov 25. pii: S0022-2836(17)30561-2. doi:, 10.1016/j.jmb.2017.11.011. PMID:29183787 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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