1w60

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{{STRUCTURE_1w60| PDB=1w60 | SCENE= }}
{{STRUCTURE_1w60| PDB=1w60 | SCENE= }}
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'''NATIVE HUMAN PCNA'''
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===NATIVE HUMAN PCNA===
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==Overview==
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The interactions between the tumor suppressor protein p21WAF1 and the cyclin-dependent kinase (CDK) complexes and with proliferating cell nuclear antigen (PCNA) regulate and coordinate the processes of cell-cycle progression and DNA replication. We present the x-ray crystal structure of PCNA complexed with a 16-mer peptide related to p21 that binds with a Kd of 100 nM. Two additional crystal structures of native PCNA provide previously undescribed structures of uncomplexed human PCNA and show that significant changes on ligand binding include rigidification of a number of flexible regions on the surface of PCNA. In the competitive binding experiments described here, we show that a 20-mer sequence from p21 can be associated simultaneously with PCNA and CDK/cyclin complexes. A structural model for this quaternary complex is presented in which the C-terminal sequence of p21 acts like double-sided tape and docks to both the PCNA and cyclin molecules. The quaternary complex shows little direct interaction between PCNA and cyclin, giving p21 the role of an adaptor molecule. Taken together, the biochemical and structural results delineate a druggable inhibitor site on the surface of PCNA that may be exploited in the design of peptidomimetics, which will act independently of cyclin-groove inhibitors.
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(as it appears on PubMed at http://www.pubmed.gov), where 15681588 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15681588}}
==About this Structure==
==About this Structure==
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[[Category: Processivity]]
[[Category: Processivity]]
[[Category: Replication]]
[[Category: Replication]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:12:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:21:26 2008''

Revision as of 02:21, 28 July 2008

Image:1w60.png

Template:STRUCTURE 1w60

NATIVE HUMAN PCNA

Template:ABSTRACT PUBMED 15681588

About this Structure

1W60 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural and biochemical studies of human proliferating cell nuclear antigen complexes provide a rationale for cyclin association and inhibitor design., Kontopidis G, Wu SY, Zheleva DI, Taylor P, McInnes C, Lane DP, Fischer PM, Walkinshaw MD, Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1871-6. Epub 2005 Jan 28. PMID:15681588

Page seeded by OCA on Mon Jul 28 05:21:26 2008

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