1ppy
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Native precursor of pyruvoyl dependent Aspartate decarboxylase
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 with as ligand. Active as Aspartate 1-decarboxylase, with EC number 4.1.1.11 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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- Aspartate 1-decarboxylase
- Escherichia coli
- Single protein
- Abell, C.
- Blundell, T L.
- Chirgadze, D Y.
- Kilkenny, M L.
- Lobley, C M.C.
- Matak-Vinkovic, D.
- Schmitzberger, F.
- Smith, A G.
- Vinkovic, M.
- Webb, M E.
- Witty, M.
- SO4
- Decarboxylase
- Intramolecular protein self-processing
- Pantothenate pathway