1LAP

MOLECULAR STRUCTURE OF LEUCINE AMINOPEPTIDASE AT 2.7-ANGSTROMS RESOLUTION

Summary for 1LAP

• Entry DOI: 10.2210/pdb1lap/pdb
• Descriptor: Cytosol aminopeptidase, ZINC ION (2 entities in total)
• Functional Keywords: hydrolase(alpha-aminoacylpeptide)
• Biological source: Bos taurus (cattle)
• Total number of polymer chains: 1
• Total formula weight: 53072.92

Authors

Burley, S.K.,David, P.R.,Taylor, A.,Lipscomb, W.N. (deposition date: 1990-08-01, release date: 1991-10-15, Last modification date: 2024-02-14)

Primary citation

Burley, S.K.,David, P.R.,Taylor, A.,Lipscomb, W.N.
Molecular structure of leucine aminopeptidase at 2.7-A resolution.
Proc.Natl.Acad.Sci.USA, 87:6878-6882, 1990

PubMed Abstract: The three-dimensional structure of bovine lens leucine aminopeptidase (EC 3.4.11.1) complexed with bestatin, a slow-binding inhibitor, has been solved to 3.0-A 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-A 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 A and maximal thickness of 90 A. 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 A3. The secondary structural composition is 40% alpha-helix and 19% beta-strand. The N-terminal domain (160 amino acids) mediates trimer-trimer interactions and does not appear to participate directly in catalysis. The C-terminal domain (327 amino acids) is responsible for catalysis and binds the two zinc ions, which are 2.88 A apart. The pair of metal ions is located near the edge of an eight-stranded, saddle-shaped beta-sheet. One zinc ion is coordinated by carboxylate oxygen atoms of Asp-255, Asp-332, and Glu-334 and the carbonyl oxygen of Asp-332. The other zinc ion is coordinated by the carboxylate oxygen atoms of Asp-255, Asp-273, and Glu-334. 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 A and thickness 10 A. Access to this cavity is provided by solvent channels that run along the twofold symmetry axes.

PubMed: 2395881
DOI: 10.1073/pnas.87.17.6878

Experimental method

X-RAY DIFFRACTION (2.7 Å)