2col: Difference between revisions
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New page: left|200px<br /><applet load="2col" size="450" color="white" frame="true" align="right" spinBox="true" caption="2col, resolution 2.2Å" /> '''Crystal structure ana... |
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[[Image:2col.gif|left|200px]]<br /><applet load="2col" size=" | [[Image:2col.gif|left|200px]]<br /><applet load="2col" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2col, resolution 2.2Å" /> | caption="2col, resolution 2.2Å" /> | ||
'''Crystal structure analysis of CyaA/C-Cam with Pyrophosphate'''<br /> | '''Crystal structure analysis of CyaA/C-Cam with Pyrophosphate'''<br /> | ||
==Overview== | ==Overview== | ||
CyaA is crucial for colonization by Bordetella pertussis, the etiologic | CyaA is crucial for colonization by Bordetella pertussis, the etiologic agent of whooping cough. Here we report crystal structures of the adenylyl cyclase domain (ACD) of CyaA with the C-terminal domain of calmodulin. Four discrete regions of CyaA bind calcium-loaded calmodulin with a large buried contact surface. Of those, a tryptophan residue (W242) at an alpha-helix of CyaA makes extensive contacts with the calcium-induced, hydrophobic pocket of calmodulin. Mutagenic analyses show that all four regions of CyaA contribute to calmodulin binding and the calmodulin-induced conformational change of CyaA is crucial for catalytic activation. A crystal structure of CyaA-calmodulin with adefovir diphosphate, the metabolite of an approved antiviral drug, reveals the location of catalytic site of CyaA and how adefovir diphosphate tightly binds CyaA. The ACD of CyaA shares a similar structure and mechanism of activation with anthrax edema factor (EF). However, the interactions of CyaA with calmodulin completely diverge from those of EF. This provides molecular details of how two structurally homologous bacterial toxins evolved divergently to bind calmodulin, an evolutionarily conserved calcium sensor. | ||
==About this Structure== | ==About this Structure== | ||
2COL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] with CA, MG and POP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] Full crystallographic information is available from [http:// | 2COL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=POP:'>POP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2COL OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Guo, Q.]] | [[Category: Guo, Q.]] | ||
[[Category: Shen, Y.]] | [[Category: Shen, Y.]] | ||
[[Category: Tang, W | [[Category: Tang, W J.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: lyase]] | [[Category: lyase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:50:52 2008'' | ||