1pe6
From Proteopedia
(New page: 200px<br /><applet load="1pe6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pe6, resolution 2.1Å" /> '''REFINED X-RAY STRUCTU...) |
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| - | [[Image:1pe6.gif|left|200px]]<br /><applet load="1pe6" size=" | + | [[Image:1pe6.gif|left|200px]]<br /><applet load="1pe6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pe6, resolution 2.1Å" /> | caption="1pe6, resolution 2.1Å" /> | ||
'''REFINED X-RAY STRUCTURE OF PAPAIN(DOT)E-64-C COMPLEX AT 2.1-ANGSTROMS RESOLUTION'''<br /> | '''REFINED X-RAY STRUCTURE OF PAPAIN(DOT)E-64-C COMPLEX AT 2.1-ANGSTROMS RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds | + | E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex. |
==About this Structure== | ==About this Structure== | ||
| - | 1PE6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with E6C and MOH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Lyase Lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.22.2 4.3.22.2] Full crystallographic information is available from [http:// | + | 1PE6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=E6C:'>E6C</scene> and <scene name='pdbligand=MOH:'>MOH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Lyase Lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.22.2 4.3.22.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PE6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: hydrolase (sulfhydryl proteinase)]] | [[Category: hydrolase (sulfhydryl proteinase)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:27:54 2008'' |
Revision as of 12:27, 21 February 2008
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REFINED X-RAY STRUCTURE OF PAPAIN(DOT)E-64-C COMPLEX AT 2.1-ANGSTROMS RESOLUTION
Overview
E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex.
About this Structure
1PE6 is a Single protein structure of sequence from [1] with and as ligands. Active as Lyase, with EC number 4.3.22.2 Full crystallographic information is available from OCA.
Reference
Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution., Yamamoto D, Matsumoto K, Ohishi H, Ishida T, Inoue M, Kitamura K, Mizuno H, J Biol Chem. 1991 Aug 5;266(22):14771-7. PMID:1860874
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