2W97

Crystal Structure of eIF4E Bound to Glycerol and eIF4G1 peptide

Summary for 2W97

• Entry DOI: 10.2210/pdb2w97/pdb
• Related: 1IPB 1IPC 1LJ2 1UG3 2V8W 2V8X 2V8Y
• Descriptor: EUKARYOTIC TRANSLATION INITIATION FACTOR 4E, EUKARYOTIC TRANSLATION INITIATION FACTOR 4 GAMMA 1, [[(2R,3S,4R,5R)-5-(6-AMINO-3-METHYL-4-OXO-5H-IMIDAZO[4,5-C]PYRIDIN-1-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHOXY-HYDROXY-PHOSPHORYL] PHOSPHONO HYDROGEN PHOSPHATE, ... (8 entities in total)
• Functional Keywords: protein biosynthesis, initiation factor, translation regulation, translation
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 55233.71

Authors

Brown, C.J.,Verma, C.S.,Walkinshaw, M.D.,Lane, D.P. (deposition date: 2009-01-22, release date: 2010-03-31, Last modification date: 2023-12-13)

Primary citation

Brown, C.J.,Verma, C.S.,Walkinshaw, M.D.,Lane, D.P.
Crystallization of eIF4E complexed with eIF4GI peptide and glycerol reveals distinct structural differences around the cap-binding site.
Cell Cycle, 8:1905-1911, 2009

PubMed Abstract: An X-ray crystal structure of the eIF4E peptide complex is described in which two such complexes are located in the asymmetric unit. One of these complexes has m(7)GTP bound in a conformation which has been observed in several eIF4E crystal structures, whilst the other complex is free of m(7)GTP and contains a unique glycerol. The two complexes show significant structural differences between each other in the cap-binding site. The glycerol bound structure shows a reorientation of the W102 side chain out of the cap-binding site, disordering of the W56 containing loop and rotation of the carboxyl side-chain of E103. This is accompanied by movement of the M101 side chain into a position where W56 in the m(7)GTP bound complex would otherwise occupy. Rotation of the W102 sidechain also displaces a structured water molecule to a new site. This novel conformation of eIF4E with glycerol bound is hypothesized to be an intermediate state between the apo and m(7)GTP bound forms of eIF4E. These insights should prove useful in the design of inhibitors of eIF4E for cancer therapy.

PubMed: 19440045
DOI: 10.4161/cc.8.12.8742

Experimental method

X-RAY DIFFRACTION (2.29 Å)