1aa9

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{{STRUCTURE_1aa9| PDB=1aa9 | SCENE= }}
{{STRUCTURE_1aa9| PDB=1aa9 | SCENE= }}
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'''HUMAN C-HA-RAS(1-171)(DOT)GDP, NMR, MINIMIZED AVERAGE STRUCTURE'''
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===HUMAN C-HA-RAS(1-171)(DOT)GDP, NMR, MINIMIZED AVERAGE STRUCTURE===
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==Overview==
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The backbone 1H, 13C, and 15N resonances of the c-Ha-Ras protein [a truncated version consisting of residues 1-171, Ras(1-171)] bound with GMPPNP (a slowly hydrolyzable analogue of GTP) were assigned and compared with those of the GDP-bound Ras(1-171). The backbone amide resonances of amino acid residues 10-13, 21, 31-39, 57-64, and 71 of Ras(1-171).GMPPNP, but not those of Ras(1-171).GDP, were extremely broadened, whereas other residues of Ras(1-171).GMPPNP exhibited amide resonances nearly as sharp as those of Ras(1-171). GDP. The residues exhibiting the extreme broadening, except for residues 21 and 71, are localized in three functional loop regions [loops L1, L2 (switch I), and L4 (switch II)], which are involved in hydrolysis of GTP and interactions with other proteins. From the temperature and magnetic field strength dependencies of the backbone amide resonance intensities, the extreme broadening was ascribed to the exchange at an intermediate rate on the NMR time scale. It was shown that the Ras(1-171) protein bound with GTP or GTPgammaS (another slowly hydrolyzable analogue of GTP) exhibits the same type of broadening. Therefore, it is a characteristic feature of the GTP-bound form of Ras that the L1, L2, and L4 loop regions, but not other regions, are in a rather slow interconversion between two or more stable conformers. This phenomenon, termed a "regional polysterism", of these loop regions may be related with their multifunctionality: the GTP-dependent interactions with several downstream target groups such as the Raf and RalGDS families and also with the GTPase activating protein (GAP) family. In fact, the binding of Ras(1-171).GMPPNP with the Ras-binding domain (residues 51-131) of c-Raf-1 was shown to eliminate the regional polysterism nearly completely. It was indicated, therefore, that each target/regulator selects its appropriate conformer among those presented by the "polysteric" binding interface of Ras. As the downstream target groups exhibit no apparent sequence homology to each other, it is possible that one target group prefers a conformer different from that preferred by another group. The involvement of loop L1 in the regional polysterism might suggest that the negative regulators, GAPs, bind to the polysteric binding interface (loops L2 and L4) of Ras and cooperatively select a conformer suitable for transition of the GTPase catalytic center, involving loops L1 and L4, into the highly active state.
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{{ABSTRACT_PUBMED_9230043}}
==About this Structure==
==About this Structure==
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1AA9 is a [[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=1AA9 OCA].
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1AA9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AA9 OCA].
==Reference==
==Reference==
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[[Category: Rsgi]]
[[Category: Rsgi]]
[[Category: Structural genomic]]
[[Category: Structural genomic]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:02:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 16:28:56 2008''

Revision as of 13:29, 30 June 2008

Image:1aa9.png

Template:STRUCTURE 1aa9

HUMAN C-HA-RAS(1-171)(DOT)GDP, NMR, MINIMIZED AVERAGE STRUCTURE

Template:ABSTRACT PUBMED 9230043

About this Structure

1AA9 is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

Regional polysterism in the GTP-bound form of the human c-Ha-Ras protein., Ito Y, Yamasaki K, Iwahara J, Terada T, Kamiya A, Shirouzu M, Muto Y, Kawai G, Yokoyama S, Laue ED, Walchli M, Shibata T, Nishimura S, Miyazawa T, Biochemistry. 1997 Jul 29;36(30):9109-19. PMID:9230043

Page seeded by OCA on Mon Jun 30 16:28:56 2008

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