1ao0

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[[Image:1ao0.gif|left|200px]]<br />
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[[Image:1ao0.jpg|left|200px]]<br /><applet load="1ao0" size="450" color="white" frame="true" align="right" spinBox="true"
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<applet load="1ao0" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="1ao0, resolution 2.8&Aring;" />
caption="1ao0, resolution 2.8&Aring;" />
'''GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE (PRPP) AMIDOTRANSFERASE FROM B. SUBTILIS COMPLEXED WITH ADP AND GMP'''<br />
'''GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE (PRPP) AMIDOTRANSFERASE FROM B. SUBTILIS COMPLEXED WITH ADP AND GMP'''<br />
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==About this Structure==
==About this Structure==
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1AO0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis] with MG, SF4, 5GP and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Amidophosphoribosyltransferase Amidophosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.14 2.4.2.14] Structure known Active Sites: AMA, AMB, AMC, AMD, MGA, MGB, MGC, MGD, NTA, NTB, NTC, NTD, PRA, PRB, PRC and PRD. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AO0 OCA].
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1AO0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis] with MG, SF4, 5GP and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Amidophosphoribosyltransferase Amidophosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.14 2.4.2.14] Known structural/functional Sites: <scene name='pdbsite=AMA:Allosteric Nucleotide Binding Site At Interface Of A And ...'>AMA</scene>, <scene name='pdbsite=AMB:Allosteric Nucleotide Binding Site At Interface Of A And ...'>AMB</scene>, <scene name='pdbsite=AMC:Allosteric Nucleotide Binding Site At Interface Of C And ...'>AMC</scene>, <scene name='pdbsite=AMD:Allosteric Nucleotide Binding Site At Interface Of C And ...'>AMD</scene>, <scene name='pdbsite=MGA:Mg2+ Ion Binding Site. The Mg2+ Ion Is Octahedrally Coor ...'>MGA</scene>, <scene name='pdbsite=MGB:Mg2+ Ion Binding Site. The Mg2+ Ion Is Octahedrally Coor ...'>MGB</scene>, <scene name='pdbsite=MGC:Mg2+ Ion Binding Site. The Mg2+ Ion Is Octahedrally Coor ...'>MGC</scene>, <scene name='pdbsite=MGD:Mg2+ Ion Binding Site. The Mg2+ Ion Is Octahedrally Coor ...'>MGD</scene>, <scene name='pdbsite=NTA:Ntn Type GLN Amidotransferase Catalytic Residue. This Si ...'>NTA</scene>, <scene name='pdbsite=NTB:Ntn Type GLN Amidotransferase Catalytic Residue. This Si ...'>NTB</scene>, <scene name='pdbsite=NTC:Ntn Type GLN Amidotransferase Catalytic Residue. This Si ...'>NTC</scene>, <scene name='pdbsite=NTD:Ntn Type GLN Amidotransferase Catalytic Residue. This Si ...'>NTD</scene>, <scene name='pdbsite=PRA:Dual Site Binding Site For Substrate Prpp In This And Ot ...'>PRA</scene>, <scene name='pdbsite=PRB:Dual Site Binding Site For Substrate Prpp In This And Ot ...'>PRB</scene>, <scene name='pdbsite=PRC:Dual Site Binding Site For Substrate Prpp In This And Ot ...'>PRC</scene> and <scene name='pdbsite=PRD:Dual Site Binding Site For Substrate Prpp In This And Ot ...'>PRD</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AO0 OCA].
==Reference==
==Reference==
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:49:49 2007''
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 14:18:37 2007''

Revision as of 12:08, 18 December 2007


1ao0, resolution 2.8Å

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GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE (PRPP) AMIDOTRANSFERASE FROM B. SUBTILIS COMPLEXED WITH ADP AND GMP

Overview

De novo purine nucleotide synthesis is regulated, at least in part, by, end-product inhibition of glutamine PRPP amidotransferase. An important, feature of this inhibition is the fact that certain synergistic nucleotide, pairs give more than additive inhibition. The physiological importance of, synergism is in amplifying regulation by the adenine and guanine, nucleotide end products of de novo synthesis. Using a new method to, quantitate synergism, ADP plus GMP were confirmed [Meyer, E., and Switzer, R. L. (1978) J. Biol. Chem. 254, 5397-5402] to give strong synergistic, inhibition of Bacillus subtilis glutamine PRPP amidotransferase. An X-ray, structure of the ternary enzyme.ADP.GMP complex established that ADP binds, to the allosteric A site and GMP to the catalytic C site. GMP increased, the binding affinity of ADP for the A site by approximately 20-fold., Synergism results from a specific nucleotide-nucleotide interaction that, is dependent upon a nucleoside diphosphate in the A site and a nucleoside, monophosphate in the C site. Furthermore, synergism is enhanced by the, competition between nucleotide inhibitor and PRPP substrate for the C, site. Purine base specificity results from a backbone carbonyl interaction, of Lys305' with the 6-NH2 group of adenine in the A site and a Ser347, Ogamma interaction with the 2-NH2 group of guanine in the C site. Steric, considerations favor binding of the nucleoside diphosphate to the A site., Site-directed replacements of key residues increased the nucleotide, concentrations needed for 50% inhibition and in some cases perturbed, synergism. Mutations in either of the nucleotide sites perturbed function, at both sites, supporting the important role of synergism.

About this Structure

1AO0 is a Single protein structure of sequence from Bacillus subtilis with MG, SF4, 5GP and ADP as ligands. Active as Amidophosphoribosyltransferase, with EC number 2.4.2.14 Known structural/functional Sites: , , , , , , , , , , , , , , and . Full crystallographic information is available from OCA.

Reference

Mechanism of the synergistic end-product regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase by nucleotides., Chen S, Tomchick DR, Wolle D, Hu P, Smith JL, Switzer RL, Zalkin H, Biochemistry. 1997 Sep 2;36(35):10718-26. PMID:9271502

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