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1pus

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[[Image:1pus.gif|left|200px]]
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{{STRUCTURE_1pus| PDB=1pus | SCENE= }}
{{STRUCTURE_1pus| PDB=1pus | SCENE= }}
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'''Solution Structure of the MutT Pyrophosphohydrolase Complexed with Mg(2+) and 8-oxo-dGMP, a Tightly-bound Product'''
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===Solution Structure of the MutT Pyrophosphohydrolase Complexed with Mg(2+) and 8-oxo-dGMP, a Tightly-bound Product===
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==Overview==
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To learn the structural basis for the unusually tight binding of 8-oxo-nucleotides to the MutT pyrophosphohydrolase of Escherichia coli (129 residues), the solution structure of the MutT-Mg(2+)-8-oxo-dGMP product complex (K(D) = 52 nM) was determined by standard 3-D heteronuclear NMR methods. Using 1746 NOEs (13.5 NOEs/residue) and 186 phi and psi values derived from backbone (15)N, Calpha, Halpha, and Cbeta chemical shifts, 20 converged structures were computed with NOE violations &lt;or=0.25 A and total energies &lt;or=450 kcal/mol. The pairwise root-mean-square deviations (RMSD) of backbone N, Calpha, and C' atoms for the secondary structured regions and for all residues of the 20 structures are 0.65 and 0.98 A, respectively, indicating a well-defined structure. Further refinement using residual dipolar coupling from 53 backbone N-H vectors slightly improved the RMSD values to 0.49 and 0.84 A, respectively. The secondary structures, which consisted of two alpha-helices and a five-stranded mixed beta-sheet, were indistinguishable from those of free MutT and of MutT in the quaternary MutT-Mg(2+)-(H(2)O)-AMPCPP-Mg(2+) complex. Comparisons of these three tertiary structures showed a narrowing of the hydrophobic nucleotide-binding cleft in the 8-oxo-dGMP complex resulting from a 2.5-4.5 A movement of helix I and a 1.5 A movement of helix II and loop 4 toward the cleft. The binding of 8-oxo-dGMP to MutT-Mg(2+) buries 71-78% of the surface area of the nucleotide. The 10(3.7)-fold weaker binding substrate analogue Mg(2+)-AMPCPP induced much smaller changes in tertiary structure, and MutT buried only 57% of the surface of the AMP moiety of AMPCPP. Formation of the MutT-Mg(2+)-8-oxo-dGMP complex slowed the backbone NH exchange rates of 45 residues of the enzyme by factors of 10(1)-10(6) as compared with the MutT-Mg(2+) and the MutT-Mg(2+)-dGMP complexes, suggesting a more compact structure when 8-oxo-dGMP is bound. The 10(4.6)-fold weaker binding of dGMP to MutT-Mg(2+) (K(D) = 1.8 mM) slowed the backbone exchange rates of only 20 residues and by smaller factors of approximately 10. Hence, the high affinity of MutT-Mg(2+) for 8-oxo-dGMP likely results from widespread ligand-induced conformation changes that narrow the nucleotide binding site and lower the overall free energy of the enzyme-product complex. Specific hydrogen bonding of the purine ring of 8-oxo-dGMP by the side chains of Asn-119 and Arg-78 may also contribute.
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(as it appears on PubMed at http://www.pubmed.gov), where 12939141 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12939141}}
==About this Structure==
==About this Structure==
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1PUS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PUS OCA].
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1PUS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PUS OCA].
==Reference==
==Reference==
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[[Category: Mutt pyrophosphohydrolase-metal-product complex]]
[[Category: Mutt pyrophosphohydrolase-metal-product complex]]
[[Category: Nucleoside triphosphate pyrophosphohydrolase]]
[[Category: Nucleoside triphosphate pyrophosphohydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:30:31 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:22:43 2008''

Revision as of 16:22, 27 July 2008

Image:1pus.png

Template:STRUCTURE 1pus

Solution Structure of the MutT Pyrophosphohydrolase Complexed with Mg(2+) and 8-oxo-dGMP, a Tightly-bound Product

Template:ABSTRACT PUBMED 12939141

About this Structure

1PUS is a Single protein structure of sequence from Escherichia coli. Full experimental information is available from OCA.

Reference

Solution structure and NH exchange studies of the MutT pyrophosphohydrolase complexed with Mg(2+) and 8-oxo-dGMP, a tightly bound product., Massiah MA, Saraswat V, Azurmendi HF, Mildvan AS, Biochemistry. 2003 Sep 2;42(34):10140-54. PMID:12939141

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