1PQH

Serine 25 to Threonine mutation of aspartate decarboxylase

Summary for 1PQH

• Entry DOI: 10.2210/pdb1pqh/pdb
• Related: 1PPY 1PQE 1PQF 1PT0 1PT1 1PYQ 1PYU 1aw8
• Descriptor: Aspartate 1-decarboxylase, SODIUM ION, MALONIC ACID, ... (4 entities in total)
• Functional Keywords: pyruvoyl dependent decarboxylase, protein self-processing, lyase
• Biological source: Escherichia coli
• Cellular location: Cytoplasm : P0A790
• Total number of polymer chains: 2
• Total formula weight: 31955.03

Authors

Schmitzberger, F.,Kilkenny, M.L.,Lobley, C.M.C.,Webb, M.E.,Vinkovic, M.,Matak-Vinkovic, D.,Witty, M.,Chirgadze, D.Y.,Smith, A.G.,Abell, C.,Blundell, T.L. (deposition date: 2003-06-18, release date: 2003-11-18, Last modification date: 2023-08-16)

Primary citation

Schmitzberger, F.,Kilkenny, M.L.,Lobley, C.M.C.,Webb, M.E.,Vinkovic, M.,Matak-Vinkovic, D.,Witty, M.,Chirgadze, D.Y.,Smith, A.G.,Abell, C.,Blundell, T.L.
Structural constraints on protein self-processing in L-aspartate-alpha-decarboxylase
Embo J., 22:6193-6204, 2003

PubMed Abstract: 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.

PubMed: 14633979
DOI: 10.1093/emboj/cdg575

Experimental method

X-RAY DIFFRACTION (1.29 Å)