7u6p

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 7u6p is ON HOLD until Paper Publication
+
==Structure of an intellectual disability-associated ornithine decarboxylase variant G84R==
 +
<StructureSection load='7u6p' size='340' side='right'caption='[[7u6p]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[7u6p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U6P FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7u6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u6p OCA], [https://pdbe.org/7u6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u6p RCSB], [https://www.ebi.ac.uk/pdbsum/7u6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u6p ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/DCOR_HUMAN DCOR_HUMAN]
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Ornithine decarboxylase (ODC) is a rate-limiting enzyme for the synthesis of polyamines (PAs). PAs are required for proliferation, and increased ODC activity is associated with cancer and neural over-proliferation. ODC levels and activity are therefore tightly regulated, including through the ODC-specific inhibitor, antizyme AZ1. Recently, ODC G84R has been reported as a partial loss-of-function variant that is associated with intellectual disability and seizures. However, G84 is distant from both the catalytic center and the ODC homodimerization interface. To understand how G84R modulates ODC activity, we have determined the crystal structure of ODC G84R in both the presence and the absence of the cofactor pyridoxal 5-phosphate. The structures show that the replacement of G84 by arginine leads to hydrogen bond formation of R84 with F420, the last residue of the ODC C-terminal helix, a structural element that is involved in the AZ1-mediated proteasomal degradation of ODC. In contrast, the catalytic center is essentially indistinguishable from that of wildtype ODC. We therefore reanalyzed the catalytic activity of ODC G84R and found that it is rescued when the protein is purified in the presence of a reducing agent to mimic the reducing environment of the cytoplasm. This suggests that R84 may exert its neurological effects not through reducing ODC catalytic activity but through misregulation of its AZ1-mediated proteasomal degradation.
-
Authors: Zhou, X.E., Schultz, C.R., Powell, K.S., Henrickson, A., Lamp, J., Brunzelle, J.S., Demeler, B., Vega, I.E., Bachmann, A.S., Melcher, K.
+
Structure and Enzymatic Activity of an Intellectual Disability-Associated Ornithine Decarboxylase Variant, G84R.,Zhou XE, Schultz CR, Suino Powell K, Henrickson A, Lamp J, Brunzelle JS, Demeler B, Vega IE, Bachmann AS, Melcher K ACS Omega. 2022 Sep 13;7(38):34665-34675. doi: 10.1021/acsomega.2c04702., eCollection 2022 Sep 27. PMID:36188294<ref>PMID:36188294</ref>
-
Description: Structure of an intellectual disability-associated ornithine decarboxylase variant G84R
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Zhou, X.E]]
+
<div class="pdbe-citations 7u6p" style="background-color:#fffaf0;"></div>
-
[[Category: Schultz, C.R]]
+
== References ==
-
[[Category: Melcher, K]]
+
<references/>
-
[[Category: Demeler, B]]
+
__TOC__
-
[[Category: Henrickson, A]]
+
</StructureSection>
-
[[Category: Bachmann, A.S]]
+
[[Category: Homo sapiens]]
-
[[Category: Brunzelle, J.S]]
+
[[Category: Large Structures]]
-
[[Category: Powell, K.S]]
+
[[Category: Bachmann AS]]
-
[[Category: Vega, I.E]]
+
[[Category: Brunzelle JS]]
-
[[Category: Lamp, J]]
+
[[Category: Demeler B]]
 +
[[Category: Henrickson A]]
 +
[[Category: Lamp J]]
 +
[[Category: Melcher K]]
 +
[[Category: Powell KS]]
 +
[[Category: Schultz CR]]
 +
[[Category: Vega IE]]
 +
[[Category: Zhou XE]]

Revision as of 19:20, 19 October 2022

Structure of an intellectual disability-associated ornithine decarboxylase variant G84R

PDB ID 7u6p

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools