1GBM: Alpha-lytic Protease With Met 190 Replaced By Ala Complex With Methoxysuccinyl-ala-ala-pro-phenylalanine Boronic Acid

Gly216 in the active site of the broadly specific MA190 mutant of alpha-lytic protease has been found to be remarkably tolerant of amino acid substitutions. Side-chains as large as Trp can be accommodated within the substrate-binding pocket without abolishing catalysis, and have major effects upon the substrate specificity of the enzyme. Kinetic characterization of eleven enzymatically active mutants against a panel of eight substrates clearly revealed the functional consequences of the substitutions at position 216. To understand better the structural basis for their altered specificity, the GA216 + MA190 and GL216 + MA190 mutants have been crystallized both with and without a representative series of peptide boronic acid transition-state analog inhibitors. An empirical description and non-parametric statistical analysis of structural variation among these enzyme: inhibitor complexes is presented. The roles of active site plasticity and dynamics in alpha-lytic protease function and substrate preference are also addressed. The results strongly suggest that substrate specificity determination in alpha-lytic protease is a distributed property of the active site and substrate molecule.
PDB ID: 1GBMDownload
MMDB ID: 3891
PDB Deposition Date: 1995/9/6
Updated in MMDB: 1998/11
Experimental Method:
x-ray diffraction
Resolution: 2.28  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 1GBM: dimeric; determined by author and by software (PISA)
Molecular Components in 1GBM
Label Count Molecule
Proteins (2 molecules)
Alpha-lytic Protease
Molecule annotation
Methoxysuccinyl-ala-ala-pro-phenylalanine Boronic Acid Inhibitor
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB