5lu8

CRYSTAL STRUCTURE OF YVAD-CMK BOUND HUMAN LEGUMAIN (AEP) IN COMPLEX WITH COMPOUND 11B

spinqualitylabelsall models 5lu8, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lu8 is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: 0QE, 5KN, ACE, EMC, NAG, PRD_002086, SNN, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LGMN_HUMAN Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system. Publication Abstract from PubMed delta-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-beta and tau pathology in Alzheimer's disease (AD). Here we report the therapeutic effect of an orally bioactive and brain permeable delta-secretase inhibitor in mouse models of AD. We performed a high-throughput screen and identified a non-toxic and selective delta-secretase inhibitor, termed compound 11, that specifically blocks delta-secretase but not other related cysteine proteases. Co-crystal structure analysis revealed a dual active site-directed and allosteric inhibition mode of this compound class. Chronic treatment of tau P301S and 5XFAD transgenic mice with this inhibitor reduces tau and APP cleavage, ameliorates synapse loss and augments long-term potentiation, resulting in protection of memory. Therefore, these findings demonstrate that this delta-secretase inhibitor may be an effective clinical therapeutic agent towards AD. Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer's disease.,Zhang Z, Obianyo O, Dall E, Du Y, Fu H, Liu X, Kang SS, Song M, Yu SP, Cabrele C, Schubert M, Li X, Wang JZ, Brandstetter H, Ye K Nat Commun. 2017 Mar 27;8:14740. doi: 10.1038/ncomms14740. PMID:28345579 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA