2HDN: Trypsin-Modified Elongation Factor Tu In Complex With Tetracycline At 2.8 Angstrom Resolution

Citation:
Abstract
Two crystal forms of a complex between trypsin-modified elongation factor Tu-MgGDP from Escherichia coli and the antibiotic tetracycline have been solved by X-ray diffraction analysis to resolutions of 2.8 and 2.1 A, respectively. In the P2(1) form, cocrystals were grown from a solution mixture of the protein and tetracycline. Six copies of the trypsin-modified EF-Tu-MgGDP-tetracycline complex are arranged as three sets of dimers in the asymmetric unit. In the second crystal form, tetracycline was diffused into P4(3)2(1)2 crystals, resulting in a monomeric complex in the asymmetric unit. Atomic coordinates have been refined to crystallographic R factors of 18.0% for the P2(1) form and 20.0% for the P4(3)2(1)2 form. In both complexes, tetracycline makes significant interactions with the GTPase active site of EF-Tu. The phenoldiketone moiety of tetracycline interacts directly with the Mg(2+), the alpha-phosphate group of GDP and two amino acids, Thr25 and Asp80, which are conserved in the GX(4)GKS/T and DX(2)G sequence motifs found in all GTPases and many ATPases. The molecular complementarity, previously unrecognized between invariant groups present in all GTPase/ATPases and the active moiety of tetracycline, may have wide-ranging implications for all drugs containing the phenoldiketone moiety as well as for the design of new compounds targeted against a broad range of GTPases or ATPases.
PDB ID: 2HDNDownload
MMDB ID: 42254
PDB Deposition Date: 2006/6/20
Updated in MMDB: 2007/11
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2HDN: dimeric; determined by author and by software (PISA)
Molecular Components in 2HDN
Label Count Molecule
Proteins (2 molecules)
1
Elongation Factor Ef-tu
Molecule annotation
1
Elongation Factor Ef-tu
Molecule annotation
Chemicals (4 molecules)
1
1
2
1
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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