1ypv
From Proteopedia
(New page: 200px<br /> <applet load="1ypv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ypv, resolution 1.80Å" /> '''Structure of human ...) |
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| - | [[Image:1ypv.gif|left|200px]]<br /> | + | [[Image:1ypv.gif|left|200px]]<br /><applet load="1ypv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ypv" size=" | + | |
caption="1ypv, resolution 1.80Å" /> | caption="1ypv, resolution 1.80Å" /> | ||
'''Structure of human thymidylate synthase at low salt conditions'''<br /> | '''Structure of human thymidylate synthase at low salt conditions'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human thymidylate synthase, a target in cancer chemotherapy, was | + | Human thymidylate synthase, a target in cancer chemotherapy, was crystallized from PEG 3350 with 30 mM ammonium sulfate (AS) in the crystallization medium. The crystals are isomorphous with the high-salt crystals ( approximately 2.0 M AS) and the structure has been solved and refined (R = 22.6%, R(free) = 24.3%) at 1.8 A resolution. The high- and low-AS-concentration structures are quite similar, with loop 181-197 is in the inactive conformation. Also, residues 95-106 and 129-135 (eukaryotic inserts region) show high mobility as assessed by poor electron density and high values of crystallographic temperature factors (residues 1-25 and 108-129 are disordered in both structures). The high mobility of this region may reflect the situation at physiological ionic strength. Of the four sulfate ions observed bound at 2.0 M AS, only two are present at 30 mM AS. The inactive conformation appears to be stabilized by the side chain of Val3 or a leucine residue from the disordered regions. The low-salt conditions of these crystals should be much more suitable for the study of thymidylate synthase inhibitors, especially those that utilize sulfate-binding sites to stabilize the inactive conformation of loop 181-197. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YPV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] Full crystallographic information is available from [http:// | + | 1YPV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YPV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Thymidylate synthase]] | [[Category: Thymidylate synthase]] | ||
[[Category: Lebioda, L.]] | [[Category: Lebioda, L.]] | ||
| - | [[Category: Lovelace, L | + | [[Category: Lovelace, L L.]] |
[[Category: Minor, W.]] | [[Category: Minor, W.]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
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[[Category: thymidylate synthase]] | [[Category: thymidylate synthase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:07:51 2008'' |
Revision as of 14:07, 21 February 2008
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Structure of human thymidylate synthase at low salt conditions
Contents |
Overview
Human thymidylate synthase, a target in cancer chemotherapy, was crystallized from PEG 3350 with 30 mM ammonium sulfate (AS) in the crystallization medium. The crystals are isomorphous with the high-salt crystals ( approximately 2.0 M AS) and the structure has been solved and refined (R = 22.6%, R(free) = 24.3%) at 1.8 A resolution. The high- and low-AS-concentration structures are quite similar, with loop 181-197 is in the inactive conformation. Also, residues 95-106 and 129-135 (eukaryotic inserts region) show high mobility as assessed by poor electron density and high values of crystallographic temperature factors (residues 1-25 and 108-129 are disordered in both structures). The high mobility of this region may reflect the situation at physiological ionic strength. Of the four sulfate ions observed bound at 2.0 M AS, only two are present at 30 mM AS. The inactive conformation appears to be stabilized by the side chain of Val3 or a leucine residue from the disordered regions. The low-salt conditions of these crystals should be much more suitable for the study of thymidylate synthase inhibitors, especially those that utilize sulfate-binding sites to stabilize the inactive conformation of loop 181-197.
Disease
Known disease associated with this structure: Timothy syndrome OMIM:[114205]
About this Structure
1YPV is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Thymidylate synthase, with EC number 2.1.1.45 Full crystallographic information is available from OCA.
Reference
Structure of human thymidylate synthase under low-salt conditions., Lovelace LL, Minor W, Lebioda L, Acta Crystallogr D Biol Crystallogr. 2005 May;61(Pt 5):622-7. Epub 2005, Apr 20. PMID:15858273
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