1wms: Difference between revisions

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[[Image:1wms.gif|left|200px]]<br />

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

<applet load="1wms" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1wms, resolution 1.25Å" />

'''High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target'''<br />

==Overview==

Rab GTPases and their effectors facilitate vesicular transport by, tethering donor vesicles to their respective target membranes. Rab9, mediates late endosome to trans-Golgi transport and has recently been, found to be a key cellular component for human immunodeficiency virus-1, Ebola, Marburg, and measles virus replication, suggesting that it may be a, novel target in the development of broad spectrum antiviral drugs. As part, of our structure-based drug design program, we have determined the crystal, structure of a C-terminally truncated human Rab9 (residues 1-177) to, 1.25-A resolution. The overall structure shows a characteristic nucleotide, binding fold consisting of a six-stranded beta-sheet surrounded by five, alpha-helices with a tightly bound GDP molecule in the active site., Structure-based sequence alignment of Rab9 with other Rab proteins reveals, that its active site consists of residues highly conserved in the Rab, GTPase family, implying a common catalytic mechanism. However, Rab9, contains seven regions that are significantly different in conformation, from other Rab proteins. Some of those regions coincide with putative, effector-binding sites and switch I and switch II regions identified by, structure/sequence alignments. The Rab9 structure at near atomic, resolution provides an excellent model for structure-based antiviral drug, design.

Rab GTPases and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. Rab9 mediates late endosome to trans-Golgi transport and has recently been found to be a key cellular component for human immunodeficiency virus-1, Ebola, Marburg, and measles virus replication, suggesting that it may be a novel target in the development of broad spectrum antiviral drugs. As part of our structure-based drug design program, we have determined the crystal structure of a C-terminally truncated human Rab9 (residues 1-177) to 1.25-A resolution. The overall structure shows a characteristic nucleotide binding fold consisting of a six-stranded beta-sheet surrounded by five alpha-helices with a tightly bound GDP molecule in the active site. Structure-based sequence alignment of Rab9 with other Rab proteins reveals that its active site consists of residues highly conserved in the Rab GTPase family, implying a common catalytic mechanism. However, Rab9 contains seven regions that are significantly different in conformation from other Rab proteins. Some of those regions coincide with putative effector-binding sites and switch I and switch II regions identified by structure/sequence alignments. The Rab9 structure at near atomic resolution provides an excellent model for structure-based antiviral drug design.

==About this Structure==

1WMS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GDP as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1WMS OCA].

1WMS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WMS OCA].

==Reference==

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[[Category: Chen, L.]]

[[Category: DiGiammarino, E.]]

[[Category: Hodge, T.W.]]

[[Category: Hodge, T W.]]

[[Category: Meehan, E.J.]]

[[Category: Meehan, E J.]]

[[Category: Toh, D.]]

[[Category: Wang, Y.]]

[[Category: Zhou, X.E.]]

[[Category: Zhou, X E.]]

[[Category: GDP]]

[[Category: gtpase]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:46:02 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1wms.gif|left|200px]]<br />
+[[Image:1wms.gif|left|200px]]<br /><applet load="1wms" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1wms" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1wms, resolution 1.25&Aring;" />
 '''High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target'''<br />
 ==Overview==
-Rab GTPases and their effectors facilitate vesicular transport by, tethering donor vesicles to their respective target membranes. Rab9, mediates late endosome to trans-Golgi transport and has recently been, found to be a key cellular component for human immunodeficiency virus-1, Ebola, Marburg, and measles virus replication, suggesting that it may be a, novel target in the development of broad spectrum antiviral drugs. As part, of our structure-based drug design program, we have determined the crystal, structure of a C-terminally truncated human Rab9 (residues 1-177) to, 1.25-A resolution. The overall structure shows a characteristic nucleotide, binding fold consisting of a six-stranded beta-sheet surrounded by five, alpha-helices with a tightly bound GDP molecule in the active site., Structure-based sequence alignment of Rab9 with other Rab proteins reveals, that its active site consists of residues highly conserved in the Rab, GTPase family, implying a common catalytic mechanism. However, Rab9, contains seven regions that are significantly different in conformation, from other Rab proteins. Some of those regions coincide with putative, effector-binding sites and switch I and switch II regions identified by, structure/sequence alignments. The Rab9 structure at near atomic, resolution provides an excellent model for structure-based antiviral drug, design.
+Rab GTPases and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. Rab9 mediates late endosome to trans-Golgi transport and has recently been found to be a key cellular component for human immunodeficiency virus-1, Ebola, Marburg, and measles virus replication, suggesting that it may be a novel target in the development of broad spectrum antiviral drugs. As part of our structure-based drug design program, we have determined the crystal structure of a C-terminally truncated human Rab9 (residues 1-177) to 1.25-A resolution. The overall structure shows a characteristic nucleotide binding fold consisting of a six-stranded beta-sheet surrounded by five alpha-helices with a tightly bound GDP molecule in the active site. Structure-based sequence alignment of Rab9 with other Rab proteins reveals that its active site consists of residues highly conserved in the Rab GTPase family, implying a common catalytic mechanism. However, Rab9 contains seven regions that are significantly different in conformation from other Rab proteins. Some of those regions coincide with putative effector-binding sites and switch I and switch II regions identified by structure/sequence alignments. The Rab9 structure at near atomic resolution provides an excellent model for structure-based antiviral drug design.
 ==About this Structure==
-WMS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GDP as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1WMS OCA].
+WMS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WMS OCA].
 ==Reference==
@@ Line 16: / Line 15: @@
 [[Category: Chen, L.]]
 [[Category: DiGiammarino, E.]]
-[[Category: Hodge, T.W.]]
+[[Category: Hodge, T W.]]
-[[Category: Meehan, E.J.]]
+[[Category: Meehan, E J.]]
 [[Category: Toh, D.]]
 [[Category: Wang, Y.]]
-[[Category: Zhou, X.E.]]
+[[Category: Zhou, X E.]]
 [[Category: GDP]]
 [[Category: gtpase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:52:34 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:46:02 2008''