2bkl
From Proteopedia
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| - | [[Image:2bkl.gif|left|200px]]<br /> | + | [[Image:2bkl.gif|left|200px]]<br /><applet load="2bkl" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2bkl" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="2bkl, resolution 1.50Å" /> | caption="2bkl, resolution 1.50Å" /> | ||
'''STRUCTURAL AND MECHANISTIC ANALYSIS OF TWO PROLYL ENDOPEPTIDASES: ROLE OF INTER-DOMAIN DYNAMICS IN CATALYSIS AND SPECIFICITY'''<br /> | '''STRUCTURAL AND MECHANISTIC ANALYSIS OF TWO PROLYL ENDOPEPTIDASES: ROLE OF INTER-DOMAIN DYNAMICS IN CATALYSIS AND SPECIFICITY'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2BKL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Myxococcus_xanthus Myxococcus xanthus] with SO4, ZAH and MES as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Prolyl_oligopeptidase Prolyl oligopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.26 3.4.21.26] | + | 2BKL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Myxococcus_xanthus Myxococcus xanthus] with SO4, ZAH and MES as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Prolyl_oligopeptidase Prolyl oligopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.26 3.4.21.26] Known structural/functional Site: <scene name='pdbsite=CAT:So4 Binding Site For Chain A'>CAT</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BKL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protease]] | [[Category: protease]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:50:13 2007'' |
Revision as of 16:40, 18 December 2007
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STRUCTURAL AND MECHANISTIC ANALYSIS OF TWO PROLYL ENDOPEPTIDASES: ROLE OF INTER-DOMAIN DYNAMICS IN CATALYSIS AND SPECIFICITY
Overview
Prolyl endopeptidases (PEPs) are a unique class of serine proteases with, considerable therapeutic potential for the treatment of celiac sprue. The, crystal structures of two didomain PEPs have been solved in alternative, configurations, thereby providing insights into the mode of action of, these enzymes. The structure of the Sphingomonas capsulata PEP, solved and, refined to 1.8-A resolution, revealed an open configuration of the active, site. In contrast, the inhibitor-bound PEP from Myxococcus xanthus was, crystallized (1.5-A resolution) in a closed form. Comparative analysis of, the two structures highlights a critical role for the domain interface in, regulating interdomain dynamics and substrate specificity. Structure-based, mutagenesis of the M. xanthus PEP confirms an important role for several, interfacial residues. A salt bridge between Arg-572 and Asp-196/Glu-197, appears to act as a latch for opening or closing the didomain enzyme, and, Arg-572 and Ile-575 may also help secure the incoming peptide substrate to, the open form of the enzyme. Arg-618 and Asp-145 are responsible for, anchoring the invariant proline residue in the active site of this, postproline-cleaving enzyme. A model is proposed for the docking of a, representative substrate PQPQLPYPQPQLP in the active site, where the, N-terminal substrate residues interact extensively with the catalytic, domain, and the C-terminal residues stretch into the propeller domain., Given the promise of the M. xanthus PEP as an oral therapeutic enzyme for, treating celiac sprue, our results provide a strong foundation for further, optimization of the PEP's clinically useful features.
About this Structure
2BKL is a Single protein structure of sequence from Myxococcus xanthus with SO4, ZAH and MES as ligands. Active as Prolyl oligopeptidase, with EC number 3.4.21.26 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structural and mechanistic analysis of two prolyl endopeptidases: role of interdomain dynamics in catalysis and specificity., Shan L, Mathews II, Khosla C, Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3599-604. Epub 2005 Feb 28. PMID:15738423
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