1v8w: Difference between revisions

Revision as of 16:32, 21 February 2008

Crystal structure analysis of the ADP-ribose pyrophosphatase of E82Q mutant, complexed with SO4 and Zn

OverviewOverview

ADP-ribose pyrophosphatase (ADPRase) catalyzes the divalent metal ion-dependent hydrolysis of ADP-ribose to ribose 5'-phosphate and AMP. This enzyme plays a key role in regulating the intracellular ADP-ribose levels, and prevents nonenzymatic ADP-ribosylation. To elucidate the pyrophosphatase hydrolysis mechanism employed by this enzyme, structural changes occurring on binding of substrate, metal and product were investigated using crystal structures of ADPRase from an extreme thermophile, Thermus thermophilus HB8. Seven structures were determined, including that of the free enzyme, the Zn(2+)-bound enzyme, the binary complex with ADP-ribose, the ternary complexes with ADP-ribose and Zn(2+) or Gd(3+), and the product complexes with AMP and Mg(2+) or with ribose 5'-phosphate and Zn(2+). The structural and functional studies suggested that the ADP-ribose hydrolysis pathway consists of four reaction states: bound with metal (I), metal and substrate (II), metal and substrate in the transition state (III), and products (IV). In reaction state II, Glu-82 and Glu-70 abstract a proton from a water molecule. This water molecule is situated at an ideal position to carry out nucleophilic attack on the adenosyl phosphate, as it is 3.6 A away from the target phosphorus and almost in line with the scissile bond.

About this StructureAbout this Structure

1V8W is a Single protein structure of sequence from Thermus thermophilus with and as ligands. Active as ADP-ribose diphosphatase, with EC number 3.6.1.13 Full crystallographic information is available from OCA.

ReferenceReference

Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal., Yoshiba S, Ooga T, Nakagawa N, Shibata T, Inoue Y, Yokoyama S, Kuramitsu S, Masui R, J Biol Chem. 2004 Aug 27;279(35):37163-74. Epub 2004 Jun 21. PMID:15210687

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 '''Crystal structure analysis of the ADP-ribose pyrophosphatase of E82Q mutant, complexed with SO4 and Zn'''<br />
 ==Overview==
-ADP-ribose pyrophosphatase (ADPRase) catalyzes the divalent metal, ion-dependent hydrolysis of ADP-ribose to ribose 5'-phosphate and AMP., This enzyme plays a key role in regulating the intracellular ADP-ribose, levels, and prevents nonenzymatic ADP-ribosylation. To elucidate the, pyrophosphatase hydrolysis mechanism employed by this enzyme, structural, changes occurring on binding of substrate, metal and product were, investigated using crystal structures of ADPRase from an extreme, thermophile, Thermus thermophilus HB8. Seven structures were determined, including that of the free enzyme, the Zn(2+)-bound enzyme, the binary, complex with ADP-ribose, the ternary complexes with ADP-ribose and Zn(2+), or Gd(3+), and the product complexes with AMP and Mg(2+) or with ribose, 5'-phosphate and Zn(2+). The structural and functional studies suggested, that the ADP-ribose hydrolysis pathway consists of four reaction states:, bound with metal (I), metal and substrate (II), metal and substrate in the, transition state (III), and products (IV). In reaction state II, Glu-82, and Glu-70 abstract a proton from a water molecule. This water molecule is, situated at an ideal position to carry out nucleophilic attack on the, adenosyl phosphate, as it is 3.6 A away from the target phosphorus and, almost in line with the scissile bond.
+ADP-ribose pyrophosphatase (ADPRase) catalyzes the divalent metal ion-dependent hydrolysis of ADP-ribose to ribose 5'-phosphate and AMP. This enzyme plays a key role in regulating the intracellular ADP-ribose levels, and prevents nonenzymatic ADP-ribosylation. To elucidate the pyrophosphatase hydrolysis mechanism employed by this enzyme, structural changes occurring on binding of substrate, metal and product were investigated using crystal structures of ADPRase from an extreme thermophile, Thermus thermophilus HB8. Seven structures were determined, including that of the free enzyme, the Zn(2+)-bound enzyme, the binary complex with ADP-ribose, the ternary complexes with ADP-ribose and Zn(2+) or Gd(3+), and the product complexes with AMP and Mg(2+) or with ribose 5'-phosphate and Zn(2+). The structural and functional studies suggested that the ADP-ribose hydrolysis pathway consists of four reaction states: bound with metal (I), metal and substrate (II), metal and substrate in the transition state (III), and products (IV). In reaction state II, Glu-82 and Glu-70 abstract a proton from a water molecule. This water molecule is situated at an ideal position to carry out nucleophilic attack on the adenosyl phosphate, as it is 3.6 A away from the target phosphorus and almost in line with the scissile bond.
 ==About this Structure==
-V8W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with SO4 and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/ADP-ribose_diphosphatase ADP-ribose diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.13 3.6.1.13] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1V8W OCA].
+V8W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/ADP-ribose_diphosphatase ADP-ribose diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.13 3.6.1.13] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V8W OCA].
 ==Reference==
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 [[Category: Nakagawa, N.]]
 [[Category: Ooga, T.]]
-[[Category: RSGI, RIKEN.Structural.Genomics/Proteomics.Initiative.]]
+[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
 [[Category: Shibata, T.]]
 [[Category: Yokoyama, S.]]
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 [[Category: structural genomics]]
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