1hpu: Difference between revisions

Revision as of 14:03, 21 February 2008

5'-NUCLEOTIDASE (CLOSED FORM), COMPLEX WITH AMPCP

OverviewOverview

5'-Nucleotidase belongs to a large superfamily of distantly related dinuclear metallophosphatases including the Ser/Thr protein phosphatases and purple acid phosphatases. The protein undergoes a 96 degrees domain rotation between an open (inactive) and a closed (active) enzyme form. Complex structures of the closed form with the products adenosine and phosphate, and with the substrate analogue inhibitor alpha,beta-methylene ADP, have been determined at 2.1 A and 1.85 A resolution, respectively. In addition, a complex of the open form of 5'-nucleotidase with ATP was analyzed at a resolution of 1.7 A. These structures show that the adenosine group binds to a specific binding pocket of the C-terminal domain. The adenine ring is stacked between Phe429 and Phe498. The N-terminal domain provides the ligands to the dimetal cluster and the conserved His117, which together form the catalytic core structure. However, the three C-terminal arginine residues 375, 379 and 410, which are involved in substrate binding, may also play a role in transition-state stabilization. The beta-phosphate group of the inhibitor is terminally coordinated to the site 2 metal ion. The site 1 metal ion coordinates a water molecule which is in an ideal position for a nucleophilic attack on the phosphorus atom, assuming an in-line mechanism of phosphoryl transfer. Another water molecule bridges the two metal ions.

About this StructureAbout this Structure

1HPU is a Single protein structure of sequence from Escherichia coli with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Mechanism of hydrolysis of phosphate esters by the dimetal center of 5'-nucleotidase based on crystal structures., Knofel T, Strater N, J Mol Biol. 2001 May 25;309(1):239-54. PMID:11491293

Page seeded by OCA on Thu Feb 21 13:03:35 2008

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OCA

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-[[Image:1hpu.gif|left|200px]]<br /><applet load="1hpu" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1hpu.gif|left|200px]]<br /><applet load="1hpu" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1hpu, resolution 1.85&Aring;" />
 '''5'-NUCLEOTIDASE (CLOSED FORM), COMPLEX WITH AMPCP'''<br />
 ==Overview==
-'-Nucleotidase belongs to a large superfamily of distantly related, dinuclear metallophosphatases including the Ser/Thr protein phosphatases, and purple acid phosphatases. The protein undergoes a 96 degrees domain, rotation between an open (inactive) and a closed (active) enzyme form., Complex structures of the closed form with the products adenosine and, phosphate, and with the substrate analogue inhibitor alpha,beta-methylene, ADP, have been determined at 2.1 A and 1.85 A resolution, respectively. In, addition, a complex of the open form of 5'-nucleotidase with ATP was, analyzed at a resolution of 1.7 A. These structures show that the, adenosine group binds to a specific binding pocket of the C-terminal, domain. The adenine ring is stacked between Phe429 and Phe498. The, N-terminal domain provides the ligands to the dimetal cluster and the, conserved His117, which together form the catalytic core structure., However, the three C-terminal arginine residues 375, 379 and 410, which, are involved in substrate binding, may also play a role in, transition-state stabilization. The beta-phosphate group of the inhibitor, is terminally coordinated to the site 2 metal ion. The site 1 metal ion, coordinates a water molecule which is in an ideal position for a, nucleophilic attack on the phosphorus atom, assuming an in-line mechanism, of phosphoryl transfer. Another water molecule bridges the two metal ions.
+'-Nucleotidase belongs to a large superfamily of distantly related dinuclear metallophosphatases including the Ser/Thr protein phosphatases and purple acid phosphatases. The protein undergoes a 96 degrees domain rotation between an open (inactive) and a closed (active) enzyme form. Complex structures of the closed form with the products adenosine and phosphate, and with the substrate analogue inhibitor alpha,beta-methylene ADP, have been determined at 2.1 A and 1.85 A resolution, respectively. In addition, a complex of the open form of 5'-nucleotidase with ATP was analyzed at a resolution of 1.7 A. These structures show that the adenosine group binds to a specific binding pocket of the C-terminal domain. The adenine ring is stacked between Phe429 and Phe498. The N-terminal domain provides the ligands to the dimetal cluster and the conserved His117, which together form the catalytic core structure. However, the three C-terminal arginine residues 375, 379 and 410, which are involved in substrate binding, may also play a role in transition-state stabilization. The beta-phosphate group of the inhibitor is terminally coordinated to the site 2 metal ion. The site 1 metal ion coordinates a water molecule which is in an ideal position for a nucleophilic attack on the phosphorus atom, assuming an in-line mechanism of phosphoryl transfer. Another water molecule bridges the two metal ions.
 ==About this Structure==
-HPU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MN and A12 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HPU OCA].
+HPU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=MN:'>MN</scene> and <scene name='pdbligand=A12:'>A12</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HPU OCA].
 ==Reference==
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 [[Category: metallophosphatase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:43:51 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:03:35 2008''