1ch8
From Proteopedia
(New page: 200px<br /><applet load="1ch8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ch8, resolution 2.5Å" /> '''STRUCTURE OF ADENYLOS...) |
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| - | [[Image:1ch8.gif|left|200px]]<br /><applet load="1ch8" size=" | + | [[Image:1ch8.gif|left|200px]]<br /><applet load="1ch8" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ch8, resolution 2.5Å" /> | caption="1ch8, resolution 2.5Å" /> | ||
'''STRUCTURE OF ADENYLOSUCCINATE SYNTHETASE FROM E. COLI COMPLEXED WITH A STRINGENT EFFECTOR, PPG2':3'P'''<br /> | '''STRUCTURE OF ADENYLOSUCCINATE SYNTHETASE FROM E. COLI COMPLEXED WITH A STRINGENT EFFECTOR, PPG2':3'P'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Guanosine 5'-diphosphate 3'-diphosphate (ppGpp), a pleiotropic effector of | + | Guanosine 5'-diphosphate 3'-diphosphate (ppGpp), a pleiotropic effector of the stringent response, potently inhibits adenylosuccinate synthetase from Escherichia coli as an allosteric effector and/or as a competitive inhibitor with respect to GTP. Crystals of the synthetase grown in the presence of IMP, hadacidin, NO3-, and Mg2+, then soaked with ppGpp, reveal electron density at the GTP pocket which is consistent with guanosine 5'-diphosphate 2':3'-cyclic monophosphate. Unlike ligand complexes of the synthetase involving IMP and GDP, the coordination of Mg2+ in this complex is octahedral with the side chain of Asp13 in the inner sphere of the cation. The cyclic phosphoryl group interacts directly with the side chain of Lys49 and indirectly through bridging water molecules with the side chains of Asn295 and Arg305. The synthetase either directly facilitates the formation of the cyclic nucleotide or scavenges trace amounts of the cyclic nucleotide from solution. Regardless of its mode of generation, the cyclic nucleotide binds far more tightly to the active site than does ppGpp. Conceivably, synthetase activity in vivo during the stringent response may be sensitive to the relative concentrations of several effectors, which together exercise precise control over the de novo synthesis of AMP. |
==About this Structure== | ==About this Structure== | ||
| - | 1CH8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with NO3, MG, GPX, HDA and IMP 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:// | + | 1CH8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=NO3:'>NO3</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=GPX:'>GPX</scene>, <scene name='pdbligand=HDA:'>HDA</scene> and <scene name='pdbligand=IMP:'>IMP</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=1CH8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cashel, M.]] | [[Category: Cashel, M.]] | ||
| - | [[Category: Fromm, H | + | [[Category: Fromm, H J.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
[[Category: Hou, Z.]] | [[Category: Hou, Z.]] | ||
[[Category: GPX]] | [[Category: GPX]] | ||
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[[Category: stringent effector]] | [[Category: stringent effector]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:06:02 2008'' |
Revision as of 10:06, 21 February 2008
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STRUCTURE OF ADENYLOSUCCINATE SYNTHETASE FROM E. COLI COMPLEXED WITH A STRINGENT EFFECTOR, PPG2':3'P
Overview
Guanosine 5'-diphosphate 3'-diphosphate (ppGpp), a pleiotropic effector of the stringent response, potently inhibits adenylosuccinate synthetase from Escherichia coli as an allosteric effector and/or as a competitive inhibitor with respect to GTP. Crystals of the synthetase grown in the presence of IMP, hadacidin, NO3-, and Mg2+, then soaked with ppGpp, reveal electron density at the GTP pocket which is consistent with guanosine 5'-diphosphate 2':3'-cyclic monophosphate. Unlike ligand complexes of the synthetase involving IMP and GDP, the coordination of Mg2+ in this complex is octahedral with the side chain of Asp13 in the inner sphere of the cation. The cyclic phosphoryl group interacts directly with the side chain of Lys49 and indirectly through bridging water molecules with the side chains of Asn295 and Arg305. The synthetase either directly facilitates the formation of the cyclic nucleotide or scavenges trace amounts of the cyclic nucleotide from solution. Regardless of its mode of generation, the cyclic nucleotide binds far more tightly to the active site than does ppGpp. Conceivably, synthetase activity in vivo during the stringent response may be sensitive to the relative concentrations of several effectors, which together exercise precise control over the de novo synthesis of AMP.
About this Structure
1CH8 is a Single protein structure of sequence from Escherichia coli with , , , and as ligands. Active as Adenylosuccinate synthase, with EC number 6.3.4.4 Full crystallographic information is available from OCA.
Reference
Effectors of the stringent response target the active site of Escherichia coli adenylosuccinate synthetase., Hou Z, Cashel M, Fromm HJ, Honzatko RB, J Biol Chem. 1999 Jun 18;274(25):17505-10. PMID:10364182
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