1sp4
From Proteopedia
(New page: 200px<br /><applet load="1sp4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sp4, resolution 2.20Å" /> '''Crystal structure of...) |
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| - | [[Image:1sp4.jpg|left|200px]]<br /><applet load="1sp4" size=" | + | [[Image:1sp4.jpg|left|200px]]<br /><applet load="1sp4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1sp4, resolution 2.20Å" /> | caption="1sp4, resolution 2.20Å" /> | ||
'''Crystal structure of NS-134 in complex with bovine cathepsin B: a two headed epoxysuccinyl inhibitor extends along the whole active site cleft'''<br /> | '''Crystal structure of NS-134 in complex with bovine cathepsin B: a two headed epoxysuccinyl inhibitor extends along the whole active site cleft'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the inhibitor NS-134 in complex with bovine | + | The crystal structure of the inhibitor NS-134 in complex with bovine cathepsin B reveals that functional groups attached to both sides of the epoxysuccinyl reactive group bind to the part of active-site cleft as predicted. The -Leu-Pro-OH side binds to the primed binding sites interacting with the His110 and His111 residues with its C-terminal carboxy group, whereas the -Leu-Gly-Meu (-Leu-Gly-Gly-OMe) part (Meu, methoxycarbonylmethyl) binds along the non-primed binding sites. Comparison with the propeptide structures of cathepsins revealed that the binding of the latter part is least similar to the procathepsin B structure; this result, together with the two-residue shift in positioning of the Leu-Gly-Gly part, suggests that the propeptide structures of the cognate enzymes may not be the best starting point for the design of reverse binding inhibitors. |
==About this Structure== | ==About this Structure== | ||
| - | 1SP4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with EPO, LEU and PRO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_B Cathepsin B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.1 3.4.22.1] Full crystallographic information is available from [http:// | + | 1SP4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=EPO:'>EPO</scene>, <scene name='pdbligand=LEU:'>LEU</scene> and <scene name='pdbligand=PRO:'>PRO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_B Cathepsin B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.1 3.4.22.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SP4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: inhibitor design]] | [[Category: inhibitor design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:03:45 2008'' |
Revision as of 13:03, 21 February 2008
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Crystal structure of NS-134 in complex with bovine cathepsin B: a two headed epoxysuccinyl inhibitor extends along the whole active site cleft
Overview
The crystal structure of the inhibitor NS-134 in complex with bovine cathepsin B reveals that functional groups attached to both sides of the epoxysuccinyl reactive group bind to the part of active-site cleft as predicted. The -Leu-Pro-OH side binds to the primed binding sites interacting with the His110 and His111 residues with its C-terminal carboxy group, whereas the -Leu-Gly-Meu (-Leu-Gly-Gly-OMe) part (Meu, methoxycarbonylmethyl) binds along the non-primed binding sites. Comparison with the propeptide structures of cathepsins revealed that the binding of the latter part is least similar to the procathepsin B structure; this result, together with the two-residue shift in positioning of the Leu-Gly-Gly part, suggests that the propeptide structures of the cognate enzymes may not be the best starting point for the design of reverse binding inhibitors.
About this Structure
1SP4 is a Protein complex structure of sequences from Bos taurus with , and as ligands. Active as Cathepsin B, with EC number 3.4.22.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of NS-134 in complex with bovine cathepsin B: a two-headed epoxysuccinyl inhibitor extends along the entire active-site cleft., Stern I, Schaschke N, Moroder L, Turk D, Biochem J. 2004 Jul 15;381(Pt 2):511-7. PMID:15084146
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