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1x1r

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(New page: 200px<br /><applet load="1x1r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x1r, resolution 1.30&Aring;" /> '''Crystal structure of...)
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[[Image:1x1r.gif|left|200px]]<br /><applet load="1x1r" size="350" color="white" frame="true" align="right" spinBox="true"
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'''Crystal structure of M-Ras in complex with GDP'''<br />
'''Crystal structure of M-Ras in complex with GDP'''<br />
==Overview==
==Overview==
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Although some members of Ras family small GTPases, including M-Ras, share, the primary structure of their effector regions with Ras, they exhibit, vastly different binding properties to Ras effectors such as c-Raf-1. We, have solved the crystal structure of M-Ras in the GDP-bound and guanosine, 5'-(beta,gamma-imido)triphosphate (Gpp(NH)p)-bound forms. The overall, structure of M-Ras resembles those of H-Ras and Rap2A, except that, M-Ras-Gpp(NH)p exhibits a distinctive switch I conformation, which is, caused by impaired intramolecular interactions between Thr-45, (corresponding to Thr-35 of H-Ras) of the effector region and the, gamma-phosphate of Gpp(NH)p. Previous 31P NMR studies showed that, H-Ras-Gpp(NH)p exists in two interconverting conformations, states 1 and, 2. Whereas state 2 is a predominant form of H-Ras and corresponds to the, "on" conformation found in the complex with effectors, state 1 is thought, to represent the "off" conformation, whose tertiary structure remains, unknown. 31P NMR analysis shows that free M-Ras-Gpp(NH)p predominantly, assumes the state 1 conformation, which undergoes conformational, transition to state 2 upon association with c-Raf-1. These results, indicate that the solved structure of M-Ras-Gp-p(NH)p corresponds to the, state 1 conformation. The predominance of state 1 in M-Ras is likely to, account for its weak binding ability to the Ras effectors, suggesting the, importance of the tertiary structure factor in small GTPase-effector, interaction. Further, the first determination of the state 1 structure, provides a molecular basis for developing novel anti-cancer drugs as, compounds that hold Ras in the state 1 "off" conformation.
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Although some members of Ras family small GTPases, including M-Ras, share the primary structure of their effector regions with Ras, they exhibit vastly different binding properties to Ras effectors such as c-Raf-1. We have solved the crystal structure of M-Ras in the GDP-bound and guanosine 5'-(beta,gamma-imido)triphosphate (Gpp(NH)p)-bound forms. The overall structure of M-Ras resembles those of H-Ras and Rap2A, except that M-Ras-Gpp(NH)p exhibits a distinctive switch I conformation, which is caused by impaired intramolecular interactions between Thr-45 (corresponding to Thr-35 of H-Ras) of the effector region and the gamma-phosphate of Gpp(NH)p. Previous 31P NMR studies showed that H-Ras-Gpp(NH)p exists in two interconverting conformations, states 1 and 2. Whereas state 2 is a predominant form of H-Ras and corresponds to the "on" conformation found in the complex with effectors, state 1 is thought to represent the "off" conformation, whose tertiary structure remains unknown. 31P NMR analysis shows that free M-Ras-Gpp(NH)p predominantly assumes the state 1 conformation, which undergoes conformational transition to state 2 upon association with c-Raf-1. These results indicate that the solved structure of M-Ras-Gp-p(NH)p corresponds to the state 1 conformation. The predominance of state 1 in M-Ras is likely to account for its weak binding ability to the Ras effectors, suggesting the importance of the tertiary structure factor in small GTPase-effector interaction. Further, the first determination of the state 1 structure provides a molecular basis for developing novel anti-cancer drugs as compounds that hold Ras in the state 1 "off" conformation.
==About this Structure==
==About this Structure==
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1X1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1X1R OCA].
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1X1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X1R OCA].
==Reference==
==Reference==
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[[Category: gtp-binding]]
[[Category: gtp-binding]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 05:47:38 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:50:12 2008''

Revision as of 13:50, 21 February 2008

Image:1x1r.gif

1x1r, resolution 1.30Å

Drag the structure with the mouse to rotate

Crystal structure of M-Ras in complex with GDP

Overview

Although some members of Ras family small GTPases, including M-Ras, share the primary structure of their effector regions with Ras, they exhibit vastly different binding properties to Ras effectors such as c-Raf-1. We have solved the crystal structure of M-Ras in the GDP-bound and guanosine 5'-(beta,gamma-imido)triphosphate (Gpp(NH)p)-bound forms. The overall structure of M-Ras resembles those of H-Ras and Rap2A, except that M-Ras-Gpp(NH)p exhibits a distinctive switch I conformation, which is caused by impaired intramolecular interactions between Thr-45 (corresponding to Thr-35 of H-Ras) of the effector region and the gamma-phosphate of Gpp(NH)p. Previous 31P NMR studies showed that H-Ras-Gpp(NH)p exists in two interconverting conformations, states 1 and 2. Whereas state 2 is a predominant form of H-Ras and corresponds to the "on" conformation found in the complex with effectors, state 1 is thought to represent the "off" conformation, whose tertiary structure remains unknown. 31P NMR analysis shows that free M-Ras-Gpp(NH)p predominantly assumes the state 1 conformation, which undergoes conformational transition to state 2 upon association with c-Raf-1. These results indicate that the solved structure of M-Ras-Gp-p(NH)p corresponds to the state 1 conformation. The predominance of state 1 in M-Ras is likely to account for its weak binding ability to the Ras effectors, suggesting the importance of the tertiary structure factor in small GTPase-effector interaction. Further, the first determination of the state 1 structure provides a molecular basis for developing novel anti-cancer drugs as compounds that hold Ras in the state 1 "off" conformation.

About this Structure

1X1R is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of M-Ras reveals a GTP-bound "off" state conformation of Ras family small GTPases., Ye M, Shima F, Muraoka S, Liao J, Okamoto H, Yamamoto M, Tamura A, Yagi N, Ueki T, Kataoka T, J Biol Chem. 2005 Sep 2;280(35):31267-75. Epub 2005 Jun 30. PMID:15994326

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