1h7s
From Proteopedia
(New page: 200px<br /> <applet load="1h7s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1h7s, resolution 1.95Å" /> '''N-TERMINAL 40KDA FR...) |
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| - | [[Image:1h7s.gif|left|200px]]<br /> | + | [[Image:1h7s.gif|left|200px]]<br /><applet load="1h7s" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1h7s" size=" | + | |
caption="1h7s, resolution 1.95Å" /> | caption="1h7s, resolution 1.95Å" /> | ||
'''N-TERMINAL 40KDA FRAGMENT OF HUMAN PMS2'''<br /> | '''N-TERMINAL 40KDA FRAGMENT OF HUMAN PMS2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human MutLalpha, a heterodimer of hMLH1 and hPMS2, is essential for DNA | + | Human MutLalpha, a heterodimer of hMLH1 and hPMS2, is essential for DNA mismatch repair. Inactivation of the hmlh1 or hpms2 genes by mutation or epigenesis causes genomic instability and a predisposition to hereditary non-polyposis cancer. We report here the X-ray crystal structures of the conserved N-terminal 40 kDa fragment of hPMS2, NhPMS2, and its complexes with ATPgammaS and ADP at 1.95, 2.7 and 2.7 A resolution, respectively. The NhPMS2 structures closely resemble the ATPase fragment of Escherichia coli MutL, which coordinates protein-protein interactions in mismatch repair by undergoing structural transformation upon binding of ATP. Unlike the E.coli MutL, whose ATPase activity requires protein dimerization, the monomeric form of NhPMS2 is active both in ATP hydrolysis and DNA binding. NhPMS2 is the first example of a GHL ATPase active as a monomer, suggesting that its activity may be modulated by hMLH1 in MutLalpha, and vice versa. The potential heterodimer interface revealed by crystallography provides a mutagenesis target for functional studies of MutLalpha. |
==Disease== | ==Disease== | ||
| - | Known diseases associated with this structure: Colorectal cancer, hereditary nonpolyposis, type 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600259 600259]], | + | Known diseases associated with this structure: Colorectal cancer, hereditary nonpolyposis, type 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600259 600259]], Mismatch repair cancer syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600259 600259]] |
==About this Structure== | ==About this Structure== | ||
| - | 1H7S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1H7S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H7S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Guarne, A.]] | [[Category: Guarne, A.]] | ||
| - | [[Category: Junop, M | + | [[Category: Junop, M S.]] |
[[Category: Yang, W.]] | [[Category: Yang, W.]] | ||
[[Category: ghl atpase]] | [[Category: ghl atpase]] | ||
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[[Category: mismatch repair]] | [[Category: mismatch repair]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:19 2008'' |
Revision as of 10:58, 21 February 2008
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N-TERMINAL 40KDA FRAGMENT OF HUMAN PMS2
Contents |
Overview
Human MutLalpha, a heterodimer of hMLH1 and hPMS2, is essential for DNA mismatch repair. Inactivation of the hmlh1 or hpms2 genes by mutation or epigenesis causes genomic instability and a predisposition to hereditary non-polyposis cancer. We report here the X-ray crystal structures of the conserved N-terminal 40 kDa fragment of hPMS2, NhPMS2, and its complexes with ATPgammaS and ADP at 1.95, 2.7 and 2.7 A resolution, respectively. The NhPMS2 structures closely resemble the ATPase fragment of Escherichia coli MutL, which coordinates protein-protein interactions in mismatch repair by undergoing structural transformation upon binding of ATP. Unlike the E.coli MutL, whose ATPase activity requires protein dimerization, the monomeric form of NhPMS2 is active both in ATP hydrolysis and DNA binding. NhPMS2 is the first example of a GHL ATPase active as a monomer, suggesting that its activity may be modulated by hMLH1 in MutLalpha, and vice versa. The potential heterodimer interface revealed by crystallography provides a mutagenesis target for functional studies of MutLalpha.
Disease
Known diseases associated with this structure: Colorectal cancer, hereditary nonpolyposis, type 4 OMIM:[600259], Mismatch repair cancer syndrome OMIM:[600259]
About this Structure
1H7S is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure and function of the N-terminal 40 kDa fragment of human PMS2: a monomeric GHL ATPase., Guarne A, Junop MS, Yang W, EMBO J. 2001 Oct 1;20(19):5521-31. PMID:11574484
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