1ypv
From Proteopedia
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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 PO4 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
Page seeded by OCA on Mon Nov 12 20:23:12 2007
