1ypv
From Proteopedia
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| , resolution 1.80Å | |||||||
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| Ligands: | , , | ||||||
| Gene: | TYMS, TS (Homo sapiens) | ||||||
| Activity: | Thymidylate synthase, with EC number 2.1.1.45 | ||||||
| Related: | 1HW3, 1HVY, 1HW4
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of human thymidylate synthase at low salt conditions
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.
About this Structure
1YPV is a Single protein structure of sequence from Homo sapiens. 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 Mar 31 01:17:14 2008
