2foz: Difference between revisions

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[[Image:2foz.gif|left|200px]]<br />

[[Image:2foz.gif|left|200px]]<br /><applet load="2foz" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="2foz" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="2foz, resolution 1.60Å" />

'''human ADP-ribosylhydrolase 3'''<br />

==Overview==

Posttranslational modifications are used by cells from all kingdoms of, life to control enzymatic activity and to regulate protein function. For, many cellular processes, including DNA repair, spindle function, and, apoptosis, reversible mono- and polyADP-ribosylation constitutes a very, important regulatory mechanism. Moreover, many pathogenic bacteria secrete, toxins which ADP-ribosylate human proteins, causing diseases such as, whooping cough, cholera, and diphtheria. Whereas the 3D structures of, numerous ADP-ribosylating toxins and related mammalian enzymes have been, elucidated, virtually nothing is known about the structure of protein, de-ADP-ribosylating enzymes. Here, we report the 3Dstructure of human, ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3, constitutes the archetype of an all-alpha-helical protein fold and, provides insights into the reversibility of protein ADP-ribosylation. Two, magnesium ions flanked by highly conserved amino acids pinpoint the, active-site crevice. Recombinant hARH3 binds free ADP-ribose with, micromolar affinity and efficiently de-ADP-ribosylates poly- but not, monoADP-ribosylated proteins. Docking experiments indicate a possible, binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our, results underscore the importance of endogenous ADP-ribosylation cycles, and provide a basis for structure-based design of ADP-ribosylhydrolase, inhibitors.

Posttranslational modifications are used by cells from all kingdoms of life to control enzymatic activity and to regulate protein function. For many cellular processes, including DNA repair, spindle function, and apoptosis, reversible mono- and polyADP-ribosylation constitutes a very important regulatory mechanism. Moreover, many pathogenic bacteria secrete toxins which ADP-ribosylate human proteins, causing diseases such as whooping cough, cholera, and diphtheria. Whereas the 3D structures of numerous ADP-ribosylating toxins and related mammalian enzymes have been elucidated, virtually nothing is known about the structure of protein de-ADP-ribosylating enzymes. Here, we report the 3Dstructure of human ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3 constitutes the archetype of an all-alpha-helical protein fold and provides insights into the reversibility of protein ADP-ribosylation. Two magnesium ions flanked by highly conserved amino acids pinpoint the active-site crevice. Recombinant hARH3 binds free ADP-ribose with micromolar affinity and efficiently de-ADP-ribosylates poly- but not monoADP-ribosylated proteins. Docking experiments indicate a possible binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our results underscore the importance of endogenous ADP-ribosylation cycles and provide a basis for structure-based design of ADP-ribosylhydrolase inhibitors.

==About this Structure==

2FOZ 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 MG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2FOZ OCA].

2FOZ 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=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FOZ OCA].

==Reference==

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Line 15:

[[Category: Koch-Nolte, F.]]

[[Category: Mueller-Dieckmann, C.]]

[[Category: Weiss, M.S.]]

[[Category: Weiss, M S.]]

[[Category: MG]]

[[Category: all alpha-helical]]

[[Category: metal binding]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 22~~:08:~~59 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:23:43 2008''

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@@ Line 1: / Line 1: @@
-[[Image:2foz.gif|left|200px]]<br />
+[[Image:2foz.gif|left|200px]]<br /><applet load="2foz" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2foz" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2foz, resolution 1.60&Aring;" />
 '''human ADP-ribosylhydrolase 3'''<br />
 ==Overview==
-Posttranslational modifications are used by cells from all kingdoms of, life to control enzymatic activity and to regulate protein function. For, many cellular processes, including DNA repair, spindle function, and, apoptosis, reversible mono- and polyADP-ribosylation constitutes a very, important regulatory mechanism. Moreover, many pathogenic bacteria secrete, toxins which ADP-ribosylate human proteins, causing diseases such as, whooping cough, cholera, and diphtheria. Whereas the 3D structures of, numerous ADP-ribosylating toxins and related mammalian enzymes have been, elucidated, virtually nothing is known about the structure of protein, de-ADP-ribosylating enzymes. Here, we report the 3Dstructure of human, ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3, constitutes the archetype of an all-alpha-helical protein fold and, provides insights into the reversibility of protein ADP-ribosylation. Two, magnesium ions flanked by highly conserved amino acids pinpoint the, active-site crevice. Recombinant hARH3 binds free ADP-ribose with, micromolar affinity and efficiently de-ADP-ribosylates poly- but not, monoADP-ribosylated proteins. Docking experiments indicate a possible, binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our, results underscore the importance of endogenous ADP-ribosylation cycles, and provide a basis for structure-based design of ADP-ribosylhydrolase, inhibitors.
+Posttranslational modifications are used by cells from all kingdoms of life to control enzymatic activity and to regulate protein function. For many cellular processes, including DNA repair, spindle function, and apoptosis, reversible mono- and polyADP-ribosylation constitutes a very important regulatory mechanism. Moreover, many pathogenic bacteria secrete toxins which ADP-ribosylate human proteins, causing diseases such as whooping cough, cholera, and diphtheria. Whereas the 3D structures of numerous ADP-ribosylating toxins and related mammalian enzymes have been elucidated, virtually nothing is known about the structure of protein de-ADP-ribosylating enzymes. Here, we report the 3Dstructure of human ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3 constitutes the archetype of an all-alpha-helical protein fold and provides insights into the reversibility of protein ADP-ribosylation. Two magnesium ions flanked by highly conserved amino acids pinpoint the active-site crevice. Recombinant hARH3 binds free ADP-ribose with micromolar affinity and efficiently de-ADP-ribosylates poly- but not monoADP-ribosylated proteins. Docking experiments indicate a possible binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our results underscore the importance of endogenous ADP-ribosylation cycles and provide a basis for structure-based design of ADP-ribosylhydrolase inhibitors.
 ==About this Structure==
-FOZ 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 MG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FOZ OCA].
+FOZ 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=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FOZ OCA].
 ==Reference==
@@ Line 16: / Line 15: @@
 [[Category: Koch-Nolte, F.]]
 [[Category: Mueller-Dieckmann, C.]]
-[[Category: Weiss, M.S.]]
+[[Category: Weiss, M S.]]
 [[Category: MG]]
 [[Category: all alpha-helical]]
 [[Category: metal binding]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:08:59 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:23:43 2008''