The 1.7 angstrom crystal structure of BPI: A study of how two dissimilar amino acid sequences can adopt the same fold

We have extended the resolution of the crystal structure of human bacterici dal/permeability-increasing protein (BPI) to 1.7 Angstrom. BPI has two doma ins with the same fold, but with little sequence similarity. To under stand the similarity in structure of the two domains, we compare the correspondi ng residue positions in the two domains by the method of 3D-1D profiles. A 3D-1D profile is a string formed by assigning each position in the 3D struc ture to one of 18 environment classes. The environment classes are defined by the local secondary structure, the area of the residue which is buried f rom solvent, and the fraction of the area buried by polar atoms. A structur al alignment between the two BPI domains was used to compare the 3D-1D envi ronments of structurally equivalent positions. Greater than 31% of the alig ned positions have conserved 3D-1D environments, but only 13% have conserve d residue identities. Analysis of the 3D-1D environmentally conserved posit ions helps to identify pairs of residues likely to be important in conservi ng the fold, regardless of the residue similarity. We find examples of 3D-1 D environmentally conserved positions with dissimilar residues which nevert heless play similar structural roles. To generalize our findings, we analyz ed four other proteins with similar structures yet dissimilar sequences. To gether, these examples show that aligned pairs of dissimilar residues often share similar structural roles, stabilizing dissimilar sequences in the sa me fold. (C) 2000 Academic Press.