1mez
From Proteopedia
(New page: 200px<br /><applet load="1mez" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mez, resolution 2.4Å" /> '''Structure of the Reco...) |
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| - | [[Image:1mez.jpg|left|200px]]<br /><applet load="1mez" size=" | + | [[Image:1mez.jpg|left|200px]]<br /><applet load="1mez" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1mez, resolution 2.4Å" /> | caption="1mez, resolution 2.4Å" /> | ||
'''Structure of the Recombinant Mouse-Muscle Adenylosuccinate Synthetase Complexed with SAMP, GDP, SO4(2-), and Mg(2+)'''<br /> | '''Structure of the Recombinant Mouse-Muscle Adenylosuccinate Synthetase Complexed with SAMP, GDP, SO4(2-), and Mg(2+)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Adenylosuccinate synthetase governs the committed step of AMP | + | Adenylosuccinate synthetase governs the committed step of AMP biosynthesis, the generation of 6-phosphoryl-IMP from GTP and IMP followed by the formation of adenylosuccinate from 6-phosphoryl-IMP and l-aspartate. The enzyme is subject to feedback inhibition by AMP and adenylosuccinate, but crystallographic complexes of the mouse muscle synthetase presented here infer mechanisms of inhibition that involve potentially synergistic ligand combinations. AMP alone adopts the productive binding mode of IMP and yet stabilizes the active site in a conformation that favors the binding of Mg(2+)-IMP to the GTP pocket. On the other hand, AMP, in the presence of GDP, orthophosphate, and Mg(2+), adopts the binding mode of adenylosuccinate. Depending on circumstances then, AMP behaves as an analogue of IMP or as an analogue of adenylosuccinate. The complex of adenylosuccinate.GDP.Mg(2+).sulfate, the first structure of an adenylosuccinate-bound synthetase, reveals significant geometric distortions and tight nonbonded contacts relevant to the proposed catalytic mechanism. Adenylosuccinate forms from 6-phosphoryl-IMP and l-aspartate by the movement of the purine ring into the alpha-amino group of l-aspartate. |
==About this Structure== | ==About this Structure== | ||
| - | 1MEZ 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, SO4, GDP and 2SA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenylosuccinate_synthase Adenylosuccinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.4 6.3.4.4] Full crystallographic information is available from [http:// | + | 1MEZ 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>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=GDP:'>GDP</scene> and <scene name='pdbligand=2SA:'>2SA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenylosuccinate_synthase Adenylosuccinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.4 6.3.4.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MEZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Borza, T.]] | [[Category: Borza, T.]] | ||
| - | [[Category: Fromm, H | + | [[Category: Fromm, H J.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
| - | [[Category: Iancu, C | + | [[Category: Iancu, C V.]] |
[[Category: 2SA]] | [[Category: 2SA]] | ||
[[Category: GDP]] | [[Category: GDP]] | ||
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[[Category: purine biosynthesis]] | [[Category: purine biosynthesis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:37 2008'' |
Revision as of 11:54, 21 February 2008
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Structure of the Recombinant Mouse-Muscle Adenylosuccinate Synthetase Complexed with SAMP, GDP, SO4(2-), and Mg(2+)
Overview
Adenylosuccinate synthetase governs the committed step of AMP biosynthesis, the generation of 6-phosphoryl-IMP from GTP and IMP followed by the formation of adenylosuccinate from 6-phosphoryl-IMP and l-aspartate. The enzyme is subject to feedback inhibition by AMP and adenylosuccinate, but crystallographic complexes of the mouse muscle synthetase presented here infer mechanisms of inhibition that involve potentially synergistic ligand combinations. AMP alone adopts the productive binding mode of IMP and yet stabilizes the active site in a conformation that favors the binding of Mg(2+)-IMP to the GTP pocket. On the other hand, AMP, in the presence of GDP, orthophosphate, and Mg(2+), adopts the binding mode of adenylosuccinate. Depending on circumstances then, AMP behaves as an analogue of IMP or as an analogue of adenylosuccinate. The complex of adenylosuccinate.GDP.Mg(2+).sulfate, the first structure of an adenylosuccinate-bound synthetase, reveals significant geometric distortions and tight nonbonded contacts relevant to the proposed catalytic mechanism. Adenylosuccinate forms from 6-phosphoryl-IMP and l-aspartate by the movement of the purine ring into the alpha-amino group of l-aspartate.
About this Structure
1MEZ is a Single protein structure of sequence from Mus musculus with , , and as ligands. Active as Adenylosuccinate synthase, with EC number 6.3.4.4 Full crystallographic information is available from OCA.
Reference
Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase., Iancu CV, Borza T, Fromm HJ, Honzatko RB, J Biol Chem. 2002 Oct 25;277(43):40536-43. Epub 2002 Aug 16. PMID:12186864
Page seeded by OCA on Thu Feb 21 13:54:37 2008
Categories: Adenylosuccinate synthase | Mus musculus | Single protein | Borza, T. | Fromm, H J. | Honzatko, R B. | Iancu, C V. | 2SA | GDP | MG | SO4 | Gtp-binding | Multigene family | Purine biosynthesis
