4zgy

STRUCTURE of HUMAN ORNITHINE DECARBOXYLASE IN COMPLEX WITH A C-TERMINAL FRAGMENT OF ANTIZYMESTRUCTURE of HUMAN ORNITHINE DECARBOXYLASE IN COMPLEX WITH A C-TERMINAL FRAGMENT OF ANTIZYME

Structural highlights 4zgy is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 1d7k Gene: ODC1 (HUMAN), OAZ1, OAZ (HUMAN) Activity: Ornithine decarboxylase, with EC number 4.1.1.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [OAZ1_HUMAN] Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake by binding to and targeting ODC1 for degradation (PubMed:17900240). Stabilizes AZIN2 by interfering with its ubiquitination. Also inhibits cellular uptake of polyamines by inactivating the polyamine uptake transporter. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. Involved in the translocation of AZNI2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol. Publication Abstract from PubMed Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins antizyme isoform 1 (Az1) and antizyme inhibitor (AzIN). Az1 suppresses polyamine production by inhibiting the assembly of the functional ODC homodimer and, most uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by competing with ODC for Az1 binding. The structural basis of the Az1-mediated regulation of polyamine homeostasis has remained elusive. Here we report crystal structures of human Az1 complexed with either ODC or AzIN. Structural analysis revealed that Az1 sterically blocks ODC homodimerization. Moreover, Az1 binding triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC, which illustrates how a substrate protein may be primed upon association with Az1 for ubiquitin-independent proteasome recognition. Dynamic and functional analyses further indicated that the Az1-induced binding and degradation of ODC by proteasome can be decoupled, with the intrinsically disordered C-terminal tail fragment of ODC being required only for degradation but not binding. Finally, the AzIN-Az1 structure suggests how AzIN may effectively compete with ODC for Az1 to restore polyamine production. Taken together, our findings offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation. Structural basis of antizyme-mediated regulation of polyamine homeostasis.,Wu HY, Chen SF, Hsieh JY, Chou F, Wang YH, Lin WT, Lee PY, Yu YJ, Lin LY, Lin TS, Lin CL, Liu GY, Tzeng SR, Hung HC, Chan NL Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11229-34. doi:, 10.1073/pnas.1508187112. Epub 2015 Aug 24. PMID:26305948 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4zgy, resolution 2.63Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image