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4zgz

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Revision as of 17:59, 16 November 2017

STRUCTURE OF HUMAN ANTIZYME INHIBITOR IN COMPLEX WITH A C-TERMINAL FRAGMENT OF ANTIZYME

Structural highlights

4zgz is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4qcg, 3btn
Gene:	AZIN1, OAZI, OAZIN (HUMAN), OAZ1, OAZ (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AZIN1_HUMAN] Antizyme inhibitor protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake by counteracting the negative effect of antizyme OAZ1, OAZ2 and OAZ3 on ODC1 activity (PubMed:17900240). Inhibits antizyme-dependent ODC degradation by binding to antizymes. Releases ODC1 from its inactive complex with antizymes, leading to formation of the catalytically active ODC1.^[1] [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.^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kanerva K, Makitie LT, Pelander A, Heiskala M, Andersson LC. Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase. Biochem J. 2008 Jan 1;409(1):187-92. PMID:17900240 doi:http://dx.doi.org/10.1042/BJ20071004
↑ Lin Y, Martin J, Gruendler C, Farley J, Meng X, Li BY, Lechleider R, Huff C, Kim RH, Grasser WA, Paralkar V, Wang T. A novel link between the proteasome pathway and the signal transduction pathway of the bone morphogenetic proteins (BMPs). BMC Cell Biol. 2002 Jun 21;3:15. PMID:12097147
↑ Kanerva K, Makitie LT, Pelander A, Heiskala M, Andersson LC. Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase. Biochem J. 2008 Jan 1;409(1):187-92. PMID:17900240 doi:http://dx.doi.org/10.1042/BJ20071004
↑ 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. Structural basis of antizyme-mediated regulation of polyamine homeostasis. 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 doi:http://dx.doi.org/10.1073/pnas.1508187112

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4zgz"

@@ Line 1: / Line 1: @@
 ==STRUCTURE OF HUMAN ANTIZYME INHIBITOR IN COMPLEX WITH A C-TERMINAL FRAGMENT OF ANTIZYME==
 <StructureSection load='4zgz' size='340' side='right' caption='[[4zgz]], [[Resolution|resolution]] 5.81&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4zgz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZGZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZGZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4zgz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZGZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZGZ FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qcg|4qcg]], [[3btn|3btn]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zgz OCA], [http://pdbe.org/4zgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zgz RCSB], [http://www.ebi.ac.uk/pdbsum/4zgz PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AZIN1, OAZI, OAZIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), OAZ1, OAZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zgz OCA], [http://pdbe.org/4zgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zgz RCSB], [http://www.ebi.ac.uk/pdbsum/4zgz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zgz ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Chan, N L]]
 [[Category: Chen, S F]]

4zgz

From Proteopedia

Revision as of 17:59, 16 November 2017

STRUCTURE OF HUMAN ANTIZYME INHIBITOR IN COMPLEX WITH A C-TERMINAL FRAGMENT OF ANTIZYME

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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