1YPV

Structure of human thymidylate synthase at low salt conditions

Summary for 1YPV

• Entry DOI: 10.2210/pdb1ypv/pdb
• Related: 1HVY 1HW3 1HW4
• Descriptor: Thymidylate synthase, PHOSPHATE ION (3 entities in total)
• Functional Keywords: thymidylate synthase, methyltransferase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 36227.32

Authors

Lovelace, L.L.,Minor, W.,Lebioda, L. (deposition date: 2005-01-31, release date: 2005-04-26, Last modification date: 2022-04-13)

Primary citation

Lovelace, L.L.,Minor, W.,Lebioda, L.
Structure of human thymidylate synthase under low-salt conditions.
Acta Crystallogr.,Sect.D, 61:622-627, 2005

PubMed Abstract: 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.

PubMed: 15858273
DOI: 10.1107/S0907444905005895

Experimental method

X-RAY DIFFRACTION (1.8 Å)