1i58: Difference between revisions

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[[Image:1i58.gif|left|200px]]<br /><applet load="1i58" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1i58.gif|left|200px]]<br /><applet load="1i58" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1i58, resolution 1.60Å" />

'''STRUCTURE OF THE HISTIDINE KINASE CHEA ATP-BINDING DOMAIN IN COMPLEX WITH ATP ANALOG ADPCP AND MAGNESIUM'''<br />

==Overview==

To probe the structural basis for protein histidine kinase (PHK) catalytic, activity and the prospects for PHK-specific inhibitor design, we report, the crystal structures for the nucleotide binding domain of Thermotoga, maritima CheA with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP), bound with either Mg(2+) or Mn(2+). The conformation of ADPNP bound to, CheA and related ATPases differs from that reported in the ADPNP complex, of PHK EnvZ. Interactions of the active site with the nucleotide, gamma-phosphate and its associated Mg(2+) ion are linked to conformational, changes in an ATP-lid that could mediate recognition of the substrate, domain. The inhibitor TNP-ATP binds CheA with its phosphates in a, nonproductive conformation and its adenine and trinitrophenyl groups in, two adjacent binding pockets. The trinitrophenyl interaction may be, exploited for designing CheA-targeted drugs that would not interfere with, host ATPases.

To probe the structural basis for protein histidine kinase (PHK) catalytic activity and the prospects for PHK-specific inhibitor design, we report the crystal structures for the nucleotide binding domain of Thermotoga maritima CheA with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP) bound with either Mg(2+) or Mn(2+). The conformation of ADPNP bound to CheA and related ATPases differs from that reported in the ADPNP complex of PHK EnvZ. Interactions of the active site with the nucleotide gamma-phosphate and its associated Mg(2+) ion are linked to conformational changes in an ATP-lid that could mediate recognition of the substrate domain. The inhibitor TNP-ATP binds CheA with its phosphates in a nonproductive conformation and its adenine and trinitrophenyl groups in two adjacent binding pockets. The trinitrophenyl interaction may be exploited for designing CheA-targeted drugs that would not interfere with host ATPases.

==About this Structure==

1I58 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with ACT, MG, ACP and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1I58 OCA].

1I58 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ACP:'>ACP</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I58 OCA].

==Reference==

Line 13:

[[Category: Single protein]]

[[Category: Thermotoga maritima]]

[[Category: Bilwes, A.M.]]

[[Category: Bilwes, A M.]]

[[Category: Crane, B.R.]]

[[Category: Crane, B R.]]

[[Category: Croal, L.R.]]

[[Category: Croal, L R.]]

[[Category: Quezada, C.M.]]

[[Category: Quezada, C M.]]

[[Category: Simon, M.I.]]

[[Category: Simon, M I.]]

[[Category: ACP]]

[[Category: ACT]]

Line 24:

[[Category: beta-alpha sandwich]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Tue Nov 20 17~~:03:~~51 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:08:07 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1i58.gif|left|200px]]<br /><applet load="1i58" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1i58.gif|left|200px]]<br /><applet load="1i58" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1i58, resolution 1.60&Aring;" />
 '''STRUCTURE OF THE HISTIDINE KINASE CHEA ATP-BINDING DOMAIN IN COMPLEX WITH ATP ANALOG ADPCP AND MAGNESIUM'''<br />
 ==Overview==
-To probe the structural basis for protein histidine kinase (PHK) catalytic, activity and the prospects for PHK-specific inhibitor design, we report, the crystal structures for the nucleotide binding domain of Thermotoga, maritima CheA with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP), bound with either Mg(2+) or Mn(2+). The conformation of ADPNP bound to, CheA and related ATPases differs from that reported in the ADPNP complex, of PHK EnvZ. Interactions of the active site with the nucleotide, gamma-phosphate and its associated Mg(2+) ion are linked to conformational, changes in an ATP-lid that could mediate recognition of the substrate, domain. The inhibitor TNP-ATP binds CheA with its phosphates in a, nonproductive conformation and its adenine and trinitrophenyl groups in, two adjacent binding pockets. The trinitrophenyl interaction may be, exploited for designing CheA-targeted drugs that would not interfere with, host ATPases.
+To probe the structural basis for protein histidine kinase (PHK) catalytic activity and the prospects for PHK-specific inhibitor design, we report the crystal structures for the nucleotide binding domain of Thermotoga maritima CheA with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP) bound with either Mg(2+) or Mn(2+). The conformation of ADPNP bound to CheA and related ATPases differs from that reported in the ADPNP complex of PHK EnvZ. Interactions of the active site with the nucleotide gamma-phosphate and its associated Mg(2+) ion are linked to conformational changes in an ATP-lid that could mediate recognition of the substrate domain. The inhibitor TNP-ATP binds CheA with its phosphates in a nonproductive conformation and its adenine and trinitrophenyl groups in two adjacent binding pockets. The trinitrophenyl interaction may be exploited for designing CheA-targeted drugs that would not interfere with host ATPases.
 ==About this Structure==
-I58 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with ACT, MG, ACP and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1I58 OCA].
+I58 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ACP:'>ACP</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I58 OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Single protein]]
 [[Category: Thermotoga maritima]]
-[[Category: Bilwes, A.M.]]
+[[Category: Bilwes, A M.]]
-[[Category: Crane, B.R.]]
+[[Category: Crane, B R.]]
-[[Category: Croal, L.R.]]
+[[Category: Croal, L R.]]
-[[Category: Quezada, C.M.]]
+[[Category: Quezada, C M.]]
-[[Category: Simon, M.I.]]
+[[Category: Simon, M I.]]
 [[Category: ACP]]
 [[Category: ACT]]
@@ Line 24: / Line 24: @@
 [[Category: beta-alpha sandwich]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 17:03:51 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:08:07 2008''