3dab

From Proteopedia

Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain

Structural highlights

3dab is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MDM4_HUMAN Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.^[1] ^[2]

Evolutionary Conservation

Checkto colour the structure by Evolutionary Conservation, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The Mdmx oncoprotein has only recently emerged as a critical-independent to Mdm2-regulator of p53 activation. We have determined the crystal structure of the N-terminal domain of human Mdmx bound to a 15-residue transactivation domain peptide of human p53. The structure shows why antagonists of the Mdm2 binding to p53 are ineffective in the Mdmx-p53 interaction.

Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain.,Popowicz GM, Czarna A, Holak TA Cell Cycle. 2008 Aug;7(15):2441-3. Epub 2008 May 27. PMID:18677113^[3]

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

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Citations

reviews cite this structure

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References

↑ Chen L, Gilkes DM, Pan Y, Lane WS, Chen J. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. EMBO J. 2005 Oct 5;24(19):3411-22. Epub 2005 Sep 15. PMID:16163388 doi:10.1038/sj.emboj.7600812
↑ Jin Y, Dai MS, Lu SZ, Xu Y, Luo Z, Zhao Y, Lu H. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J. 2006 Mar 22;25(6):1207-18. Epub 2006 Mar 2. PMID:16511572 doi:10.1038/sj.emboj.7601010
↑ Popowicz GM, Czarna A, Holak TA. Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain. Cell Cycle. 2008 Aug;7(15):2441-3. Epub 2008 May 27. PMID:18677113