3bcn
From Proteopedia
(New page: 200px<br /><applet load="3bcn" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bcn, resolution 2.85Å" /> '''Crystal structure of...) |
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==Overview== | ==Overview== | ||
| - | Multiple proteases of the same family are quite often present in the same | + | Multiple proteases of the same family are quite often present in the same species in biological systems. These multiple proteases, despite having high homology in their primary and tertiary structures, show deviations in properties such as stability, activity, and specificity. It is of interest, therefore, to compare the structures of these multiple proteases in a single species to identify the structural changes, if any, that may be responsible for such deviations. Ervatamin-A, ervatamin-B and ervatamin-C are three such papain-like cysteine proteases found in the latex of the tropical plant Ervatamia coronaria, and are known not only for their high stability over a wide range of temperature and pH, but also for variations in activity and specificity among themselves and among other members of the family. Here we report the crystal structures of ervatamin-A and ervatamin-C, complexed with an irreversible inhibitor 1-[l-N-(trans-epoxysuccinyl)leucyl]amino-4-guanidinobutane (E-64), together with enzyme kinetics and molecular dynamic simulation studies. A comparison of these results with the earlier structures helps in a correlation of the structural features with the corresponding functional properties. The specificity constants (k(cat)/K(m)) for the ervatamins indicate that all of these enzymes have specificity for a branched hydrophobic residue at the P2 position of the peptide substrates, with different degrees of efficiency. A single amino acid change, as compared to ervatamin-C, in the S2 pocket of ervatamin-A (Ala67-->Tyr) results in a 57-fold increase in its k(cat)/K(m) value for a substrate having a Val at the P2 position. Our studies indicate a higher enzymatic activity of ervatamin-A, which has been subsequently explained at the molecular level from the three-dimensional structure of the enzyme and in the context of its helix polarizibility and active site plasticity. |
==About this Structure== | ==About this Structure== | ||
| - | 3BCN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Tabernaemontana_divaricata Tabernaemontana divaricata] with <scene name='pdbligand=E64:'>E64</scene> and <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 3BCN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Tabernaemontana_divaricata Tabernaemontana divaricata] with <scene name='pdbligand=E64:'>E64</scene> and <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 2PSC. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Biswas, S.]] | [[Category: Biswas, S.]] | ||
[[Category: Chakrabarti, C.]] | [[Category: Chakrabarti, C.]] | ||
| - | [[Category: Dattagupta, J | + | [[Category: Dattagupta, J K.]] |
[[Category: Ghosh, R.]] | [[Category: Ghosh, R.]] | ||
[[Category: BME]] | [[Category: BME]] | ||
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[[Category: thiol protease]] | [[Category: thiol protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:04:53 2008'' |
Revision as of 17:04, 21 February 2008
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Crystal structure of a papain-like cysteine protease Ervatamin-A complexed with irreversible inhibitor E-64
Overview
Multiple proteases of the same family are quite often present in the same species in biological systems. These multiple proteases, despite having high homology in their primary and tertiary structures, show deviations in properties such as stability, activity, and specificity. It is of interest, therefore, to compare the structures of these multiple proteases in a single species to identify the structural changes, if any, that may be responsible for such deviations. Ervatamin-A, ervatamin-B and ervatamin-C are three such papain-like cysteine proteases found in the latex of the tropical plant Ervatamia coronaria, and are known not only for their high stability over a wide range of temperature and pH, but also for variations in activity and specificity among themselves and among other members of the family. Here we report the crystal structures of ervatamin-A and ervatamin-C, complexed with an irreversible inhibitor 1-[l-N-(trans-epoxysuccinyl)leucyl]amino-4-guanidinobutane (E-64), together with enzyme kinetics and molecular dynamic simulation studies. A comparison of these results with the earlier structures helps in a correlation of the structural features with the corresponding functional properties. The specificity constants (k(cat)/K(m)) for the ervatamins indicate that all of these enzymes have specificity for a branched hydrophobic residue at the P2 position of the peptide substrates, with different degrees of efficiency. A single amino acid change, as compared to ervatamin-C, in the S2 pocket of ervatamin-A (Ala67-->Tyr) results in a 57-fold increase in its k(cat)/K(m) value for a substrate having a Val at the P2 position. Our studies indicate a higher enzymatic activity of ervatamin-A, which has been subsequently explained at the molecular level from the three-dimensional structure of the enzyme and in the context of its helix polarizibility and active site plasticity.
About this Structure
3BCN is a Single protein structure of sequence from Tabernaemontana divaricata with and as ligands. This structure supersedes the now removed PDB entry 2PSC. Full crystallographic information is available from OCA.
Reference
Structural insights into the substrate specificity and activity of ervatamins, the papain-like cysteine proteases from a tropical plant, Ervatamia coronaria., Ghosh R, Chakraborty S, Chakrabarti C, Dattagupta JK, Biswas S, FEBS J. 2008 Feb;275(3):421-34. Epub 2007 Dec 19. PMID:18167146
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