1nb5
From Proteopedia
(New page: 200px<br /> <applet load="1nb5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nb5, resolution 2.4Å" /> '''Crystal structure of...) |
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| - | [[Image:1nb5.gif|left|200px]]<br /> | + | [[Image:1nb5.gif|left|200px]]<br /><applet load="1nb5" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1nb5, resolution 2.4Å" /> | caption="1nb5, resolution 2.4Å" /> | ||
'''Crystal structure of stefin A in complex with cathepsin H'''<br /> | '''Crystal structure of stefin A in complex with cathepsin H'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Binding of cystatin-type inhibitors to papain-like exopeptidases cannot be | + | Binding of cystatin-type inhibitors to papain-like exopeptidases cannot be explained by the stefin B-papain complex. The crystal structure of human stefin A bound to an aminopeptidase, porcine cathepsin H, has been determined in monoclinic and orthorhombic crystal forms at 2.8A and 2.4A resolutions, respectively. The asymmetric unit of each form contains four complexes. The structures are similar to the stefin B-papain complex, but with a few distinct differences. On binding, the N-terminal residues of stefin A adopt the form of a hook, which pushes away cathepsin H mini-chain residues and distorts the structure of the short four residue insertion (Lys155A-Asp155D) unique to cathepsin H. Comparison with the structure of isolated cathepsin H shows that the rims of the cathepsin H structure are slightly displaced (up to 1A) from their position in the free enzyme. Furthermore, comparison with the stefin B-papain complex showed that molecules of stefin A bind about 0.8A deeper into the active site cleft of cathepsin H than stefin B into papain. The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex. Carboxymethylation of papain seems to have prevented the formation of the genuine binding geometry between a papain-like enzyme and a cystatin-type inhibitor as we observe it in the structure presented here. |
==About this Structure== | ==About this Structure== | ||
| - | 1NB5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Active as [http://en.wikipedia.org/wiki/Cathepsin_H Cathepsin H], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.16 3.4.22.16] Full crystallographic information is available from [http:// | + | 1NB5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Active as [http://en.wikipedia.org/wiki/Cathepsin_H Cathepsin H], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.16 3.4.22.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NB5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: enzyme-inhibitor complex]] | [[Category: enzyme-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:04:17 2008'' |
Revision as of 12:04, 21 February 2008
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Crystal structure of stefin A in complex with cathepsin H
Overview
Binding of cystatin-type inhibitors to papain-like exopeptidases cannot be explained by the stefin B-papain complex. The crystal structure of human stefin A bound to an aminopeptidase, porcine cathepsin H, has been determined in monoclinic and orthorhombic crystal forms at 2.8A and 2.4A resolutions, respectively. The asymmetric unit of each form contains four complexes. The structures are similar to the stefin B-papain complex, but with a few distinct differences. On binding, the N-terminal residues of stefin A adopt the form of a hook, which pushes away cathepsin H mini-chain residues and distorts the structure of the short four residue insertion (Lys155A-Asp155D) unique to cathepsin H. Comparison with the structure of isolated cathepsin H shows that the rims of the cathepsin H structure are slightly displaced (up to 1A) from their position in the free enzyme. Furthermore, comparison with the stefin B-papain complex showed that molecules of stefin A bind about 0.8A deeper into the active site cleft of cathepsin H than stefin B into papain. The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex. Carboxymethylation of papain seems to have prevented the formation of the genuine binding geometry between a papain-like enzyme and a cystatin-type inhibitor as we observe it in the structure presented here.
About this Structure
1NB5 is a Protein complex structure of sequences from Homo sapiens and Sus scrofa. Active as Cathepsin H, with EC number 3.4.22.16 Full crystallographic information is available from OCA.
Reference
Crystal structure of Stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases., Jenko S, Dolenc I, Guncar G, Dobersek A, Podobnik M, Turk D, J Mol Biol. 2003 Feb 21;326(3):875-85. PMID:12581647
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