6x27

Lon protease proteolytic domain complexed with bortezomib

spinqualitylabelsall models 6x27, resolution 2.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6x27 is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1PE, BO2, GOL Related: 6wys, 6wzv, 6x1m Gene: LONP1, PRSS15 (HUMAN) Activity: Endopeptidase La, with EC number 3.4.21.53 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [LONM_HUMAN] ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner. May regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters. Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein.[HAMAP-Rule:MF_03120] Publication Abstract from PubMed LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression of LONP1 promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Despite the importance of LONP1 in human biology and disease, very few LONP1 inhibitors have been described in the literature. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Our efforts led to several nanomolar LONP1 inhibitors with little to no activity against the 20S proteasome that serve as tool compounds to investigate LONP1 biology. Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology.,Kingsley LJ, He X, McNeill M, Nelson J, Nikulin V, Ma Z, Lu W, Zhou VW, Manuia M, Kreusch A, Gao MY, Witmer D, Vaillancourt MT, Lu M, Greenblatt S, Lee C, Vashisht A, Bender S, Spraggon G, Michellys PY, Jia Y, Haling JR, Lelais G J Med Chem. 2021 Apr 6. doi: 10.1021/acs.jmedchem.0c02152. PMID:33821636 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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