Native precursor of pyruvoyl dependent Aspartate decarboxylase

File:1ppy.gif


PDB ID 1ppy

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, resolution 1.95Å
Ligands: ,
Gene: PAND OR B0131 OR C0160 OR Z0142 OR ECS0135 OR SF0128 (Escherichia coli)
Activity: Aspartate 1-decarboxylase, with EC number 4.1.1.11
Related: 1aw8


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



OverviewOverview

Aspartate decarboxylase, which is translated as a pro-protein, undergoes intramolecular self-cleavage at Gly24-Ser25. We have determined the crystal structures of an unprocessed native precursor, in addition to Ala24 insertion, Ala26 insertion and Gly24-->Ser, His11-->Ala, Ser25-->Ala, Ser25-->Cys and Ser25-->Thr mutants. Comparative analyses of the cleavage site reveal specific conformational constraints that govern self-processing and demonstrate that considerable rearrangement must occur. We suggest that Thr57 Ogamma and a water molecule form an 'oxyanion hole' that likely stabilizes the proposed oxyoxazolidine intermediate. Thr57 and this water molecule are probable catalytic residues able to support acid-base catalysis. The conformational freedom in the loop preceding the cleavage site appears to play a determining role in the reaction. The molecular mechanism of self-processing, presented here, emphasizes the importance of stabilization of the oxyoxazolidine intermediate. Comparison of the structural features shows significant similarity to those in other self-processing systems, and suggests that models of the cleavage site of such enzymes based on Ser-->Ala or Ser-->Thr mutants alone may lead to erroneous interpretations of the mechanism.

About this StructureAbout this Structure

1PPY is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Structural constraints on protein self-processing in L-aspartate-alpha-decarboxylase., Schmitzberger F, Kilkenny ML, Lobley CM, Webb ME, Vinkovic M, Matak-Vinkovic D, Witty M, Chirgadze DY, Smith AG, Abell C, Blundell TL, EMBO J. 2003 Dec 1;22(23):6193-204. PMID:14633979

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