1mq7
From Proteopedia
(New page: 200px<br /><applet load="1mq7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mq7, resolution 1.95Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1mq7.gif|left|200px]]<br /><applet load="1mq7" size=" | + | [[Image:1mq7.gif|left|200px]]<br /><applet load="1mq7" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1mq7, resolution 1.95Å" /> | caption="1mq7, resolution 1.95Å" /> | ||
'''CRYSTAL STRUCTURE OF DUTPASE FROM MYCOBACTERIUM TUBERCULOSIS (RV2697C)'''<br /> | '''CRYSTAL STRUCTURE OF DUTPASE FROM MYCOBACTERIUM TUBERCULOSIS (RV2697C)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of Mycobacterium tuberculosis dUTP nucleotidohydrolase | + | The structure of Mycobacterium tuberculosis dUTP nucleotidohydrolase (dUTPase) has been determined at 1.3 Angstrom resolution in complex with magnesium ion and the non-hydrolyzable substrate analog, alpha,beta-imido dUTP. dUTPase is an enzyme essential for depleting potentially toxic concentrations of dUTP in the cell. Given the importance of its biological role, it has been proposed that inhibiting M.tuberculosis dUTPase might be an effective means to treat tuberculosis infection in humans. The crystal structure presented here offers some insight into the potential for designing a specific inhibitor of the M.tuberculosis dUTPase enzyme. The structure also offers new insights into the mechanism of dUTP hydrolysis by providing an accurate representation of the enzyme-substrate complex in which both the metal ion and dUTP analog are included. The structure suggests that inclusion of a magnesium ion is important for stabilizing the position of the alpha-phosphorus for an in-line nucleophilic attack. In the absence of magnesium, the alpha-phosphate of dUTP can have either of the two positions which differ by 4.5 Angstrom. A transiently ordered C-terminal loop further assists catalysis by shielding the general base, Asp83, from solvent thus elevating its pK(a) so that it might in turn activate a tightly bound water molecule for nucleophilic attack. The metal ion coordinates alpha, beta, and gamma phosphate groups with tridentate geometry identical with that observed in the crystal structure of DNA polymerase beta complexed with magnesium and dNTP analog, revealing some common features in catalytic mechanism. |
==About this Structure== | ==About this Structure== | ||
| - | 1MQ7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with TRS as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] Full crystallographic information is available from [http:// | + | 1MQ7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=TRS:'>TRS</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MQ7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: dUTP diphosphatase]] | [[Category: dUTP diphosphatase]] | ||
[[Category: Chan, S.]] | [[Category: Chan, S.]] | ||
| - | [[Category: Cho, U | + | [[Category: Cho, U S.]] |
[[Category: Eisenberg, D.]] | [[Category: Eisenberg, D.]] | ||
[[Category: Heike, K.]] | [[Category: Heike, K.]] | ||
[[Category: Lekin, T.]] | [[Category: Lekin, T.]] | ||
[[Category: Naranjo, C.]] | [[Category: Naranjo, C.]] | ||
| - | [[Category: Perry, L | + | [[Category: Perry, L J.]] |
| - | [[Category: Sawaya, M | + | [[Category: Sawaya, M R.]] |
| - | [[Category: Segelke, B | + | [[Category: Segelke, B W.]] |
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
| - | [[Category: Yeates, T | + | [[Category: Yeates, T O.]] |
[[Category: TRS]] | [[Category: TRS]] | ||
[[Category: jelly-roll]] | [[Category: jelly-roll]] | ||
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[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:57:54 2008'' |
Revision as of 11:57, 21 February 2008
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CRYSTAL STRUCTURE OF DUTPASE FROM MYCOBACTERIUM TUBERCULOSIS (RV2697C)
Overview
The structure of Mycobacterium tuberculosis dUTP nucleotidohydrolase (dUTPase) has been determined at 1.3 Angstrom resolution in complex with magnesium ion and the non-hydrolyzable substrate analog, alpha,beta-imido dUTP. dUTPase is an enzyme essential for depleting potentially toxic concentrations of dUTP in the cell. Given the importance of its biological role, it has been proposed that inhibiting M.tuberculosis dUTPase might be an effective means to treat tuberculosis infection in humans. The crystal structure presented here offers some insight into the potential for designing a specific inhibitor of the M.tuberculosis dUTPase enzyme. The structure also offers new insights into the mechanism of dUTP hydrolysis by providing an accurate representation of the enzyme-substrate complex in which both the metal ion and dUTP analog are included. The structure suggests that inclusion of a magnesium ion is important for stabilizing the position of the alpha-phosphorus for an in-line nucleophilic attack. In the absence of magnesium, the alpha-phosphate of dUTP can have either of the two positions which differ by 4.5 Angstrom. A transiently ordered C-terminal loop further assists catalysis by shielding the general base, Asp83, from solvent thus elevating its pK(a) so that it might in turn activate a tightly bound water molecule for nucleophilic attack. The metal ion coordinates alpha, beta, and gamma phosphate groups with tridentate geometry identical with that observed in the crystal structure of DNA polymerase beta complexed with magnesium and dNTP analog, revealing some common features in catalytic mechanism.
About this Structure
1MQ7 is a Single protein structure of sequence from Mycobacterium tuberculosis with as ligand. Active as dUTP diphosphatase, with EC number 3.6.1.23 Full crystallographic information is available from OCA.
Reference
Crystal structure of the Mycobacterium tuberculosis dUTPase: insights into the catalytic mechanism., Chan S, Segelke B, Lekin T, Krupka H, Cho US, Kim MY, So M, Kim CY, Naranjo CM, Rogers YC, Park MS, Waldo GS, Pashkov I, Cascio D, Perry JL, Sawaya MR, J Mol Biol. 2004 Aug 6;341(2):503-17. PMID:15276840
Page seeded by OCA on Thu Feb 21 13:57:54 2008
Categories: Mycobacterium tuberculosis | Single protein | DUTP diphosphatase | Chan, S. | Cho, U S. | Eisenberg, D. | Heike, K. | Lekin, T. | Naranjo, C. | Perry, L J. | Sawaya, M R. | Segelke, B W. | TBSGC, TB Structural Genomics Consortium. | Yeates, T O. | TRS | Jelly-roll | Protein structure initiative | Psi | Structural genomics | Tb structural genomics consortium | Tbsgc
