1t1s
From Proteopedia
(New page: 200px<br /><applet load="1t1s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t1s, resolution 2.4Å" /> '''Crystal Structure of ...) |
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| - | [[Image:1t1s.jpg|left|200px]]<br /><applet load="1t1s" size=" | + | [[Image:1t1s.jpg|left|200px]]<br /><applet load="1t1s" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1t1s, resolution 2.4Å" /> | caption="1t1s, resolution 2.4Å" /> | ||
'''Crystal Structure of the Reductoisomerase Complexed with a Bisphosphonate'''<br /> | '''Crystal Structure of the Reductoisomerase Complexed with a Bisphosphonate'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have obtained the single-crystal X-ray crystallographic structures of the bisphosphonates [(1-isoquinolinylamino)methylene]-1,1-bisphosphonate and [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate, bound to the enzyme 1-deoxyxylulose-5-phosphate reductoisomerase (DXR, EC 1.1.1.267, also known as 2-C-methyl- | + | We have obtained the single-crystal X-ray crystallographic structures of the bisphosphonates [(1-isoquinolinylamino)methylene]-1,1-bisphosphonate and [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate, bound to the enzyme 1-deoxyxylulose-5-phosphate reductoisomerase (DXR, EC 1.1.1.267, also known as 2-C-methyl-d-erythritol-4-phosphate synthase), an important target for the development of antimalarial drugs. Our results indicate that both bisphosphonates bind into the fosmidomycin binding site. The aromatic groups are in a shallow hydrophobic pocket, and the phosphonate groups are involved in electrostatic interactions with Mg2+ or a cluster of carboxylic acid groups and lysine while the fosmidomycin phosphonate-binding site is occupied by a sulfate ion (as also observed in the DXR/NADP+ structure). The availability of these two new crystal structures opens up the possibility of the further development of bisphosphonates and related systems as DXR inhibitors and, potentially, as antiinfective agents. |
==About this Structure== | ==About this Structure== | ||
| - | 1T1S 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 SO4, MG and CBQ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/1-deoxy-D-xylulose-5-phosphate_reductoisomerase 1-deoxy-D-xylulose-5-phosphate reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.267 1.1.1.267] Full crystallographic information is available from [http:// | + | 1T1S 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=SO4:'>SO4</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=CBQ:'>CBQ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/1-deoxy-D-xylulose-5-phosphate_reductoisomerase 1-deoxy-D-xylulose-5-phosphate reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.267 1.1.1.267] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Ohsawa, K.]] | [[Category: Ohsawa, K.]] | ||
[[Category: Oldfield, E.]] | [[Category: Oldfield, E.]] | ||
| - | [[Category: Sanders, J | + | [[Category: Sanders, J M.]] |
[[Category: Wiesner, J.]] | [[Category: Wiesner, J.]] | ||
[[Category: Yajima, S.]] | [[Category: Yajima, S.]] | ||
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[[Category: three domains]] | [[Category: three domains]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:09:01 2008'' |
Revision as of 13:09, 21 February 2008
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Crystal Structure of the Reductoisomerase Complexed with a Bisphosphonate
Overview
We have obtained the single-crystal X-ray crystallographic structures of the bisphosphonates [(1-isoquinolinylamino)methylene]-1,1-bisphosphonate and [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate, bound to the enzyme 1-deoxyxylulose-5-phosphate reductoisomerase (DXR, EC 1.1.1.267, also known as 2-C-methyl-d-erythritol-4-phosphate synthase), an important target for the development of antimalarial drugs. Our results indicate that both bisphosphonates bind into the fosmidomycin binding site. The aromatic groups are in a shallow hydrophobic pocket, and the phosphonate groups are involved in electrostatic interactions with Mg2+ or a cluster of carboxylic acid groups and lysine while the fosmidomycin phosphonate-binding site is occupied by a sulfate ion (as also observed in the DXR/NADP+ structure). The availability of these two new crystal structures opens up the possibility of the further development of bisphosphonates and related systems as DXR inhibitors and, potentially, as antiinfective agents.
About this Structure
1T1S is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as 1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267 Full crystallographic information is available from OCA.
Reference
Crystallographic structures of two bisphosphonate:1-deoxyxylulose-5-phosphate reductoisomerase complexes., Yajima S, Hara K, Sanders JM, Yin F, Ohsawa K, Wiesner J, Jomaa H, Oldfield E, J Am Chem Soc. 2004 Sep 8;126(35):10824-5. PMID:15339150
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