2V8H: Crystal Structure Of Mutant E159a Of Beta-Alanine Synthase From Saccharomyces Kluyveri In Complex With Its Substrate N-Carbamyl-Beta-Alanine

Citation:
Abstract
Beta-alanine synthase is the final enzyme of the reductive pyrimidine catabolic pathway, which is responsible for the breakdown of uracil and thymine in higher organisms. The fold of the homodimeric enzyme from the yeast Saccharomyces kluyveri identifies it as a member of the AcyI/M20 family of metallopeptidases. Its subunit consists of a catalytic domain harboring a di-zinc center and a smaller dimerization domain. The present site-directed mutagenesis studies identify Glu(159) and Arg(322) as crucial for catalysis and His(262) and His(397) as functionally important but not essential. We determined the crystal structures of wild-type beta-alanine synthase in complex with the reaction product beta-alanine, and of the mutant E159A with the substrate N-carbamyl-beta-alanine, revealing the closed state of a dimeric AcyI/M20 metallopeptidase-like enzyme. Subunit closure is achieved by a approximately 30 degrees rigid body domain rotation, which completes the active site by integration of substrate binding residues that belong to the dimerization domain of the same or the partner subunit. Substrate binding is achieved via a salt bridge, a number of hydrogen bonds, and coordination to one of the zinc ions of the di-metal center.
PDB ID: 2V8HDownload
MMDB ID: 59796
PDB Deposition Date: 2007/8/8
Updated in MMDB: 2007/12
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 2V8H: dimeric; determined by author and by software (PISA)
Molecular Components in 2V8H
Label Count Molecule
Proteins (2 molecules)
2
Beta-alanine Synthase
Molecule annotation
Chemicals (8 molecules)
1
4
2
2
3
2
* Click molecule labels to explore molecular sequence information.

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