1P7I

CRYSTAL STRUCTURE OF ENGRAILED HOMEODOMAIN MUTANT K52A

Summary for 1P7I

• Entry DOI: 10.2210/pdb1p7i/pdb
• Related: 1DUO 1ENH 2HDD 3HDD
• Descriptor: Segmentation polarity homeobox protein engrailed, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID (3 entities in total)
• Functional Keywords: dna binding protein
• Biological source: Drosophila melanogaster (fruit fly)
• Cellular location: Nucleus: P02836
• Total number of polymer chains: 4
• Total formula weight: 28867.95

Authors

Stollar, E.J.,Mayor, U.,Lovell, S.C.,Federici, L.,Freund, S.M.,Fersht, A.R.,Luisi, B.F. (deposition date: 2003-05-02, release date: 2003-10-14, Last modification date: 2023-08-16)

Primary citation

Stollar, E.J.,Mayor, U.,Lovell, S.C.,Federici, L.,Freund, S.M.,Fersht, A.R.,Luisi, B.F.
Crystal Structures of Engrailed Homeodomain Mutants: IMPLICATIONS FOR STABILITY AND DYNAMICS
J.Biol.Chem., 278:43699-43708, 2003

PubMed Abstract: We report the crystal structures and biophysical characterization of two stabilized mutants of the Drosophila Engrailed homeodomain that have been engineered to minimize electrostatic repulsion. Four independent copies of each mutant occupy the crystal lattice, and comparison of these structures illustrates variation that can be partly ascribed to networks of correlated conformational adjustments. Central to one network is leucine 26 (Leu26), which occupies alternatively two side chain rotameric conformations (-gauche and trans) and different positions within the hydrophobic core. Similar sets of conformational substates are observed in other Engrailed structures and in another homeodomain. The pattern of structural adjustments can account for NMR relaxation data and sequence co-variation networks in the wider homeodomain family. It may also explain the dysfunction associated with a P26L mutation in the human ARX homeodomain protein. Finally, we observe a novel dipolar interaction between a conserved tryptophan and a water molecule positioned along the normal to the indole ring. This interaction may explain the distinctive fluorescent properties of the homeodomain family.

PubMed: 12923178
DOI: 10.1074/jbc.M308029200

Experimental method

X-RAY DIFFRACTION (2.1 Å)