1cps: Difference between revisions

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[[Image:1cps.jpg|left|200px]]<br /><applet load="1cps" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1cps.jpg|left|200px]]<br /><applet load="1cps" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1cps, resolution 2.25Å" />

'''STRUCTURAL COMPARISON OF SULFODIIMINE AND SULFONAMIDE INHIBITORS IN THEIR COMPLEXES WITH ZINC ENZYMES'''<br />

==Overview==

The three-dimensional structure of (L(-)-2-carboxy-3-phenylpropyl), methylsulfodiimine in its complex with the zinc metalloenzyme, carboxypeptidase A has been determined at 2.25-A resolution by x-ray, crystallographic methods. This is the first example of a, sulfodiimine-containing inhibitor binding to a zinc enzyme, and the, structure of the enzyme-inhibitor complex reveals that the tetrahedral, sulfodiimine group coordinates to the active site zinc ion in unidentate, fashion. The zinc-coordinated nitrogen atom of the sulfodiimine group is, also within hydrogen bonding distance to active site base Glu-270;, presumably, the sulfodiimine is ionized and accepts a hydrogen bond from, protonated Glu-270. The other sulfodiimine nitrogen accepts a hydrogen, bond from Arg-127, and the inhibitor binds as a possible analogue of the, tetrahedral transition state (or intermediate) in a promoted water pathway, for peptide hydrolysis. The unidentate sulfodiimine-zinc binding mode, observed in this enzyme-inhibitor complex is reminiscent of that observed, in sulfonamide complexes with the zinc metalloenzyme carbonic anhydrase, II, and the structural features of sulfodiimine- and sulfonamide-zinc, interactions exhibit important similarities among recently determined, structures of enzyme-inhibitor complexes: ionized nitrogens bind to zinc, in each structure, and these nitrogens are engaged in hydrogen bond, interactions with neighboring enzyme residues.

The three-dimensional structure of (L(-)-2-carboxy-3-phenylpropyl) methylsulfodiimine in its complex with the zinc metalloenzyme carboxypeptidase A has been determined at 2.25-A resolution by x-ray crystallographic methods. This is the first example of a sulfodiimine-containing inhibitor binding to a zinc enzyme, and the structure of the enzyme-inhibitor complex reveals that the tetrahedral sulfodiimine group coordinates to the active site zinc ion in unidentate fashion. The zinc-coordinated nitrogen atom of the sulfodiimine group is also within hydrogen bonding distance to active site base Glu-270; presumably, the sulfodiimine is ionized and accepts a hydrogen bond from protonated Glu-270. The other sulfodiimine nitrogen accepts a hydrogen bond from Arg-127, and the inhibitor binds as a possible analogue of the tetrahedral transition state (or intermediate) in a promoted water pathway for peptide hydrolysis. The unidentate sulfodiimine-zinc binding mode observed in this enzyme-inhibitor complex is reminiscent of that observed in sulfonamide complexes with the zinc metalloenzyme carbonic anhydrase II, and the structural features of sulfodiimine- and sulfonamide-zinc interactions exhibit important similarities among recently determined structures of enzyme-inhibitor complexes: ionized nitrogens bind to zinc in each structure, and these nitrogens are engaged in hydrogen bond interactions with neighboring enzyme residues.

==About this Structure==

1CPS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ZN and CPM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1CPS OCA].

1CPS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=CPM:'>CPM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CPS OCA].

==Reference==

Line 14:

[[Category: Carboxypeptidase A]]

[[Category: Single protein]]

[[Category: Alexander, R.S.]]

[[Category: Alexander, R S.]]

[[Category: Cappalonga, A.M.]]

[[Category: Cappalonga, A M.]]

[[Category: Christianson, D.W.]]

[[Category: Christianson, D W.]]

[[Category: CPM]]

[[Category: ZN]]

[[Category: hydrolase(c-terminal peptidase)]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Tue Nov 20~~ 12:39:~~31 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:08:27 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1cps.jpg|left|200px]]<br /><applet load="1cps" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1cps.jpg|left|200px]]<br /><applet load="1cps" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1cps, resolution 2.25&Aring;" />
 '''STRUCTURAL COMPARISON OF SULFODIIMINE AND SULFONAMIDE INHIBITORS IN THEIR COMPLEXES WITH ZINC ENZYMES'''<br />
 ==Overview==
-The three-dimensional structure of (L(-)-2-carboxy-3-phenylpropyl), methylsulfodiimine in its complex with the zinc metalloenzyme, carboxypeptidase A has been determined at 2.25-A resolution by x-ray, crystallographic methods. This is the first example of a, sulfodiimine-containing inhibitor binding to a zinc enzyme, and the, structure of the enzyme-inhibitor complex reveals that the tetrahedral, sulfodiimine group coordinates to the active site zinc ion in unidentate, fashion. The zinc-coordinated nitrogen atom of the sulfodiimine group is, also within hydrogen bonding distance to active site base Glu-270;, presumably, the sulfodiimine is ionized and accepts a hydrogen bond from, protonated Glu-270. The other sulfodiimine nitrogen accepts a hydrogen, bond from Arg-127, and the inhibitor binds as a possible analogue of the, tetrahedral transition state (or intermediate) in a promoted water pathway, for peptide hydrolysis. The unidentate sulfodiimine-zinc binding mode, observed in this enzyme-inhibitor complex is reminiscent of that observed, in sulfonamide complexes with the zinc metalloenzyme carbonic anhydrase, II, and the structural features of sulfodiimine- and sulfonamide-zinc, interactions exhibit important similarities among recently determined, structures of enzyme-inhibitor complexes: ionized nitrogens bind to zinc, in each structure, and these nitrogens are engaged in hydrogen bond, interactions with neighboring enzyme residues.
+The three-dimensional structure of (L(-)-2-carboxy-3-phenylpropyl) methylsulfodiimine in its complex with the zinc metalloenzyme carboxypeptidase A has been determined at 2.25-A resolution by x-ray crystallographic methods. This is the first example of a sulfodiimine-containing inhibitor binding to a zinc enzyme, and the structure of the enzyme-inhibitor complex reveals that the tetrahedral sulfodiimine group coordinates to the active site zinc ion in unidentate fashion. The zinc-coordinated nitrogen atom of the sulfodiimine group is also within hydrogen bonding distance to active site base Glu-270; presumably, the sulfodiimine is ionized and accepts a hydrogen bond from protonated Glu-270. The other sulfodiimine nitrogen accepts a hydrogen bond from Arg-127, and the inhibitor binds as a possible analogue of the tetrahedral transition state (or intermediate) in a promoted water pathway for peptide hydrolysis. The unidentate sulfodiimine-zinc binding mode observed in this enzyme-inhibitor complex is reminiscent of that observed in sulfonamide complexes with the zinc metalloenzyme carbonic anhydrase II, and the structural features of sulfodiimine- and sulfonamide-zinc interactions exhibit important similarities among recently determined structures of enzyme-inhibitor complexes: ionized nitrogens bind to zinc in each structure, and these nitrogens are engaged in hydrogen bond interactions with neighboring enzyme residues.
 ==About this Structure==
-CPS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ZN and CPM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CPS OCA].
+CPS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=CPM:'>CPM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CPS OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Carboxypeptidase A]]
 [[Category: Single protein]]
-[[Category: Alexander, R.S.]]
+[[Category: Alexander, R S.]]
-[[Category: Cappalonga, A.M.]]
+[[Category: Cappalonga, A M.]]
-[[Category: Christianson, D.W.]]
+[[Category: Christianson, D W.]]
 [[Category: CPM]]
 [[Category: ZN]]
 [[Category: hydrolase(c-terminal peptidase)]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:39:31 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:08:27 2008''