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Title: Molecular structure of leucine aminopeptidase at 2. 7- angstrom resolution

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (United States)
 [1]; ;  [2];  [3]
  1. Harvard Univ., Cambridge, MA (USA) Brigham and Women's Hospital, Boston, MA (USA)
  2. Harvard Univ., Cambridge, MA (USA)
  3. Tufts Univ., Boston, MA (USA)

The three-dimensional structure of bovine lens leucine aminopeptidase complexed with bestatin, a slow-binding inhibitor, has been solved to 3.0-{angstrom} resolution by the multiple isomorphous replacement method with phase combination and density modification. In addition, the structure of the isomorphous native enzyme has been refined at 2.7-{angstrom} resolution, and the current crystallographic R factor is 0.169 for a model that includes the two zinc ions and all 487 amino acid residues comprising the asymmetric unit. The enzyme is physiologically active as a hexamer, which has 32 symmetry and is triangular in shape with a triangle edge length of 115 {angstrom} and maximal thickness of 90 {angstrom}. The monomers are crystallographically equivalent and each is folded into two unequal {alpha}/{beta} domains connected by an {alpha}-helix to give a comma-like shape with approximate maximal dimensions of 90 x 55 x 55 {angstrom}{sup 3}. The secondary structural composition is 40% {alpha}-helix and 19% {beta}-strand. The active site also contains two positively charged residues, Lys-250 and Arg-336. The six active sites are themselves located in the interior of the hexamer, where they line a disk-shaped cavity of radius 15 {angstrom} and thickness 10 {angstrom}. Access to this cavity is provided by solvent channels that run along the twofold symmetry axes.

OSTI ID:
5450107
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:17; ISSN 0027-8424
Country of Publication:
United States
Language:
English