1gvu: Difference between revisions

Revision as of 13:54, 21 February 2008

ENDOTHIAPEPSIN COMPLEX WITH H189

OverviewOverview

Endothiapepsin is derived from the fungus Endothia parasitica and is a member of the aspartic proteinase class of enzymes. This class of enzyme is comprised of two structurally similar lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The three-dimensional structures of endothiapepsin bound to five transition state analogue inhibitors (H189, H256, CP-80,794, PD-129,541 and PD-130,328) have been solved at atomic resolution allowing full anisotropic modelling of each complex. The active sites of the five structures have been studied with a view to studying the catalytic mechanism of the aspartic proteinases by locating the active site protons by carboxyl bond length differences and electron density analysis. In the CP-80,794 structure there is excellent electron density for the hydrogen on the inhibitory statine hydroxyl group which forms a hydrogen bond with the inner oxygen of Asp32. The location of this proton has implications for the catalytic mechanism of the aspartic proteinases as it is consistent with the proposed mechanism in which Asp32 is the negatively charged aspartate. A number of short hydrogen bonds (approximately 2.6 A) with ESD values of around 0.01 A that may have a role in catalysis have been identified within the active site of each structure; the lengths of these bonds have been confirmed using NMR techniques. The possibility and implications of low barrier hydrogen bonds in the active site are considered.

About this StructureAbout this Structure

1GVU is a Protein complex structure of sequences from Cryphonectria parasitica with as ligand. Active as Endothiapepsin, with EC number 3.4.23.22 Full crystallographic information is available from OCA.

ReferenceReference

Five atomic resolution structures of endothiapepsin inhibitor complexes: implications for the aspartic proteinase mechanism., Coates L, Erskine PT, Crump MP, Wood SP, Cooper JB, J Mol Biol. 2002 May 17;318(5):1405-15. PMID:12083527

Page seeded by OCA on Thu Feb 21 12:54:33 2008

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OCA

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-[[Image:1gvu.gif|left|200px]]<br /><applet load="1gvu" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1gvu.gif|left|200px]]<br /><applet load="1gvu" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1gvu, resolution 0.94&Aring;" />
 '''ENDOTHIAPEPSIN COMPLEX WITH H189'''<br />
 ==Overview==
-Endothiapepsin is derived from the fungus Endothia parasitica and is a, member of the aspartic proteinase class of enzymes. This class of enzyme, is comprised of two structurally similar lobes, each lobe contributing an, aspartic acid residue to form a catalytic dyad that acts to cleave the, substrate peptide bond. The three-dimensional structures of endothiapepsin, bound to five transition state analogue inhibitors (H189, H256, CP-80,794, PD-129,541 and PD-130,328) have been solved at atomic resolution allowing, full anisotropic modelling of each complex. The active sites of the five, structures have been studied with a view to studying the catalytic, mechanism of the aspartic proteinases by locating the active site protons, by carboxyl bond length differences and electron density analysis. In the, CP-80,794 structure there is excellent electron density for the hydrogen, on the inhibitory statine hydroxyl group which forms a hydrogen bond with, the inner oxygen of Asp32. The location of this proton has implications, for the catalytic mechanism of the aspartic proteinases as it is, consistent with the proposed mechanism in which Asp32 is the negatively, charged aspartate. A number of short hydrogen bonds (approximately 2.6 A), with ESD values of around 0.01 A that may have a role in catalysis have, been identified within the active site of each structure; the lengths of, these bonds have been confirmed using NMR techniques. The possibility and, implications of low barrier hydrogen bonds in the active site are, considered.
+Endothiapepsin is derived from the fungus Endothia parasitica and is a member of the aspartic proteinase class of enzymes. This class of enzyme is comprised of two structurally similar lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The three-dimensional structures of endothiapepsin bound to five transition state analogue inhibitors (H189, H256, CP-80,794, PD-129,541 and PD-130,328) have been solved at atomic resolution allowing full anisotropic modelling of each complex. The active sites of the five structures have been studied with a view to studying the catalytic mechanism of the aspartic proteinases by locating the active site protons by carboxyl bond length differences and electron density analysis. In the CP-80,794 structure there is excellent electron density for the hydrogen on the inhibitory statine hydroxyl group which forms a hydrogen bond with the inner oxygen of Asp32. The location of this proton has implications for the catalytic mechanism of the aspartic proteinases as it is consistent with the proposed mechanism in which Asp32 is the negatively charged aspartate. A number of short hydrogen bonds (approximately 2.6 A) with ESD values of around 0.01 A that may have a role in catalysis have been identified within the active site of each structure; the lengths of these bonds have been confirmed using NMR techniques. The possibility and implications of low barrier hydrogen bonds in the active site are considered.
 ==About this Structure==
-GVU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GVU OCA].
+GVU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GVU OCA].
 ==Reference==
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 [[Category: Protein complex]]
 [[Category: Coates, L.]]
-[[Category: Cooper, J.B.]]
+[[Category: Cooper, J B.]]
-[[Category: Crump, M.P.]]
+[[Category: Crump, M P.]]
-[[Category: Erskine, P.T.]]
+[[Category: Erskine, P T.]]
-[[Category: Wood, S.P.]]
+[[Category: Wood, S P.]]
 [[Category: SO4]]
 [[Category: anisotropic refinement]]
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 [[Category: z tetrahedral intermediate]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:18:41 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:54:33 2008''