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| '''Native precursor of pyruvoyl dependent Aspartate decarboxylase'''
| | ===Native precursor of pyruvoyl dependent Aspartate decarboxylase=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_14633979}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 14633979 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_14633979}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Intramolecular protein self-processing]] | | [[Category: Intramolecular protein self-processing]] |
| [[Category: Pantothenate pathway]] | | [[Category: Pantothenate pathway]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:21:04 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:39:48 2008'' |