1ppy: Difference between revisions

Revision as of 15:31, 21 February 2008

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

Page seeded by OCA on Thu Feb 21 14:31:16 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1ppy.gif|left|200px]]<br /><applet load="1ppy" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ppy.gif|left|200px]]<br /><applet load="1ppy" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ppy, resolution 1.95&Aring;" />
 '''Native precursor of pyruvoyl dependent Aspartate decarboxylase'''<br />
 ==Overview==
-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--&gt;Ser, His11--&gt;Ala, Ser25--&gt;Ala, Ser25--&gt;Cys and Ser25--&gt;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--&gt;Ala or, Ser--&gt;Thr mutants alone may lead to erroneous interpretations of the, mechanism.
+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--&gt;Ser, His11--&gt;Ala, Ser25--&gt;Ala, Ser25--&gt;Cys and Ser25--&gt;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--&gt;Ala or Ser--&gt;Thr mutants alone may lead to erroneous interpretations of the mechanism.
 ==About this Structure==
-PPY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Aspartate_1-decarboxylase Aspartate 1-decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.11 4.1.1.11] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PPY OCA].
+PPY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Aspartate_1-decarboxylase Aspartate 1-decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.11 4.1.1.11] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PPY OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Abell, C.]]
-[[Category: Blundell, T.L.]]
+[[Category: Blundell, T L.]]
-[[Category: Chirgadze, D.Y.]]
+[[Category: Chirgadze, D Y.]]
-[[Category: Kilkenny, M.L.]]
+[[Category: Kilkenny, M L.]]
-[[Category: Lobley, C.M.C.]]
+[[Category: Lobley, C M.C.]]
 [[Category: Matak-Vinkovic, D.]]
 [[Category: Schmitzberger, F.]]
-[[Category: Smith, A.G.]]
+[[Category: Smith, A G.]]
 [[Category: Vinkovic, M.]]
-[[Category: Webb, M.E.]]
+[[Category: Webb, M E.]]
 [[Category: Witty, M.]]
 [[Category: SO4]]
@@ Line 30: / Line 30: @@
 [[Category: pantothenate pathway]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:00:47 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:31:16 2008''