Threedimensional solution structure and backbone dynamics of a variant of human interleukin-3

The three-dimensional structure and backbone dynamics of a truncatedG.D. Searle and Company and multiply substituted recombinant human interleukin-3 (IL-3) variant700 Chesterfield (SC-65369) have been determined from multidimensional heteronuclearParkway North, St. Louis MO 63198, USA nuclear magnetic resonance spectroscopic data. Sequential application of distance geometry and restrained molecular dynamics calculations produced a family of 25 convergent structures which satisfy a total of 1812 experimental constraints (1659 proton-proton NOEs, 75 backbone dihedral angle constraints, and 39 pairs of hydrogen bond constraints) with an average root-mean-square deviation from the mean coordinate positions of 0.88(20.15) Å and 1.37(20.13) Å for the backbone and all heavy atoms, respectively, of all residues except 28 to 39. The structure is a left-handed four-helix bundle (comprised of helices A through D) with two long overhand loops (designated as loops AB and CD). Loop AB contains a short fifth helix (helix A') which is closely packed against helix D in an approximately parallel fashion and which has multiple contacts with loo