1km2: Difference between revisions
New page: left|200px<br /><applet load="1km2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1km2, resolution 1.50Å" /> '''crystal structure of... |
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[[Image:1km2.gif|left|200px]]<br /><applet load="1km2" size=" | [[Image:1km2.gif|left|200px]]<br /><applet load="1km2" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1km2, resolution 1.50Å" /> | caption="1km2, resolution 1.50Å" /> | ||
'''crystal structure of orotidine monophosphate mutant Q185A with 6-azaUMP'''<br /> | '''crystal structure of orotidine monophosphate mutant Q185A with 6-azaUMP'''<br /> | ||
==Overview== | ==Overview== | ||
The crystal structures of orotidine 5'-monophosphate decarboxylases from | The crystal structures of orotidine 5'-monophosphate decarboxylases from four different sources have been published recently. However, the detailed mechanism of catalysis of the most proficient enzyme known to date remains elusive. As the ligand-protein interactions at the orotate binding site are crucial to the understanding of this enzyme, we mutated several of the residues surrounding the aromatic part of the substrate, individually and in combination. The ensuing effects on enzyme structure and stability were characterized by X-ray crystallography of inhibitor, product, or substrate complexes and by chemical denaturation with guanidine hydrochloride, respectively. The results are consistent with the residues K42D70K72D75B being charged and forming an 'alternate charge network' around the reactive part of the substrate. In addition to exerting charge-charge repulsion on the orotate carboxylate, Asp70 also makes a crucial contribution to enzyme stability. Consequently, orotidine 5'-monophosphate decarboxylases seem to require the presence of a negative charge at this position for catalysis as well as for correct and stable folding. | ||
==About this Structure== | ==About this Structure== | ||
1KM2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus] with UP6 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] Full crystallographic information is available from [http:// | 1KM2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus] with <scene name='pdbligand=UP6:'>UP6</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KM2 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Gillon, W.]] | [[Category: Gillon, W.]] | ||
[[Category: Pai, E | [[Category: Pai, E F.]] | ||
[[Category: Wu, N.]] | [[Category: Wu, N.]] | ||
[[Category: UP6]] | [[Category: UP6]] | ||
[[Category: tim barrel]] | [[Category: tim barrel]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:35:33 2008'' | ||
Revision as of 14:35, 21 February 2008
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crystal structure of orotidine monophosphate mutant Q185A with 6-azaUMP
OverviewOverview
The crystal structures of orotidine 5'-monophosphate decarboxylases from four different sources have been published recently. However, the detailed mechanism of catalysis of the most proficient enzyme known to date remains elusive. As the ligand-protein interactions at the orotate binding site are crucial to the understanding of this enzyme, we mutated several of the residues surrounding the aromatic part of the substrate, individually and in combination. The ensuing effects on enzyme structure and stability were characterized by X-ray crystallography of inhibitor, product, or substrate complexes and by chemical denaturation with guanidine hydrochloride, respectively. The results are consistent with the residues K42D70K72D75B being charged and forming an 'alternate charge network' around the reactive part of the substrate. In addition to exerting charge-charge repulsion on the orotate carboxylate, Asp70 also makes a crucial contribution to enzyme stability. Consequently, orotidine 5'-monophosphate decarboxylases seem to require the presence of a negative charge at this position for catalysis as well as for correct and stable folding.
About this StructureAbout this Structure
1KM2 is a Single protein structure of sequence from Methanothermobacter thermautotrophicus with as ligand. Active as Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 Full crystallographic information is available from OCA.
ReferenceReference
Mapping the active site-ligand interactions of orotidine 5'-monophosphate decarboxylase by crystallography., Wu N, Gillon W, Pai EF, Biochemistry. 2002 Mar 26;41(12):4002-11. PMID:11900543
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