1zot
From Proteopedia
(New page: 200px<br /> <applet load="1zot" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zot, resolution 2.20Å" /> '''crystal structure a...) |
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| - | [[Image:1zot.gif|left|200px]]<br /> | + | [[Image:1zot.gif|left|200px]]<br /><applet load="1zot" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zot" size=" | + | |
caption="1zot, resolution 2.20Å" /> | caption="1zot, resolution 2.20Å" /> | ||
'''crystal structure analysis of the CyaA/C-Cam with PMEAPP'''<br /> | '''crystal structure analysis of the CyaA/C-Cam with PMEAPP'''<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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ZOT 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/Homo_sapiens Homo sapiens] with CA, MG and EMA 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:// | + | 1ZOT 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/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=EMA:'>EMA</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=1ZOT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Guo, Q.]] | [[Category: Guo, Q.]] | ||
| - | [[Category: Tang, W | + | [[Category: Tang, W J.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: EMA]] | [[Category: EMA]] | ||
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[[Category: pmeapp]] | [[Category: pmeapp]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:17:39 2008'' |
Revision as of 14:17, 21 February 2008
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crystal structure analysis of the CyaA/C-Cam with PMEAPP
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Cavernous malformations of CNS and retina OMIM:[604214], Cerebral cavernous malformations-1 OMIM:[604214], Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations OMIM:[604214], Leukemia, acute T-cell lymphoblastic OMIM:[603025], Leukemia, acute myeloid OMIM:[603025]
About this Structure
1ZOT is a Protein complex structure of sequences from Bordetella pertussis and Homo sapiens with , and as ligands. Active as Adenylate cyclase, with EC number 4.6.1.1 Full crystallographic information is available from OCA.
Reference
Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin., Guo Q, Shen Y, Lee YS, Gibbs CS, Mrksich M, Tang WJ, EMBO J. 2005 Sep 21;24(18):3190-201. Epub 2005 Sep 1. PMID:16138079
Page seeded by OCA on Thu Feb 21 16:17:39 2008
Categories: Adenylate cyclase | Bordetella pertussis | Homo sapiens | Protein complex | Guo, Q. | Tang, W J. | CA | EMA | MG | Adenylyl cyclase toxin | Atp | Calmodulin-binding | Cyaa | Pmeapp
