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

Journal Article · Sat Sep 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.17.6878· OSTI ID:5450107

Burley, S K ^[1]; David, P R; Lipscomb, W N ^[2]; Taylor, A ^[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), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:17; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550602* -- Medicine-- External Radiation in Diagnostics-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
AMINOPEPTIDASES
CARBOXYLIC ACIDS
COHERENT SCATTERING
CRYSTALLOGRAPHY
DIFFRACTION
ENZYME ACTIVITY
ENZYMES
HYDROLASES
LEUCINE
MOLECULAR STRUCTURE
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
SCATTERING
X-RAY DIFFRACTION