5est
From Proteopedia
(New page: 200px<br /><applet load="5est" size="450" color="white" frame="true" align="right" spinBox="true" caption="5est, resolution 2.09Å" /> '''CRYSTALLOGRAPHIC ANA...) |
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| - | [[Image:5est.gif|left|200px]]<br /><applet load="5est" size=" | + | [[Image:5est.gif|left|200px]]<br /><applet load="5est" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="5est, resolution 2.09Å" /> | caption="5est, resolution 2.09Å" /> | ||
'''CRYSTALLOGRAPHIC ANALYSIS OF THE INHIBITION OF PORCINE PANCREATIC ELASTASE BY A PEPTIDYL BORONIC ACID: STRUCTURE OF A REACTION INTERMEDIATE'''<br /> | '''CRYSTALLOGRAPHIC ANALYSIS OF THE INHIBITION OF PORCINE PANCREATIC ELASTASE BY A PEPTIDYL BORONIC ACID: STRUCTURE OF A REACTION INTERMEDIATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of porcine pancreatic elastase (PPE) complexed to | + | The crystal structure of porcine pancreatic elastase (PPE) complexed to carbobenzoxy-alanylisoleucine-boronic acid (ZAIB) is reported to 2.09-A resolution and refined to an R factor of 0.15. This is the first reported structural analysis of PPE with an isoleucine residu in the primary specificity pocket. The results include (1) marked displacement of the inhibitor out of the active site leading to (2) a close (2.2 A) direct contact between B (boron atom of the inhibitor) and N epsilon of His-57 and also (3) covalent bonding (1.5 A) to O gamma of Ser-195. A scheme for the mechanism of inhibition of PPE by ZAIB is proposed. A comparison with a peptidyl difluoromethyl ketone-PPE complex (Ki = 9.5 microns) is made to explain the strong inhibition of PPE by ZAIB (Ki = 0.3 micron). These results lead us to characterize this structure as a time- and space-averaged reaction intermediate, providing fresh insight into the cramped dimensions available in enzymatic catalyses. |
==About this Structure== | ==About this Structure== | ||
| - | 5EST is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with SO4 and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] Full crystallographic information is available from [http:// | + | 5EST is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EST OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Pancreatic elastase]] | [[Category: Pancreatic elastase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Meyerjunior, E | + | [[Category: Meyerjunior, E F.]] |
[[Category: Radhakrishnan, R.]] | [[Category: Radhakrishnan, R.]] | ||
| - | [[Category: Rosenfieldjunior, R | + | [[Category: Rosenfieldjunior, R E.]] |
| - | [[Category: Takahashi, L | + | [[Category: Takahashi, L H.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: hydrolase(serine proteinase)]] | [[Category: hydrolase(serine proteinase)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:15:12 2008'' |
Revision as of 17:15, 21 February 2008
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CRYSTALLOGRAPHIC ANALYSIS OF THE INHIBITION OF PORCINE PANCREATIC ELASTASE BY A PEPTIDYL BORONIC ACID: STRUCTURE OF A REACTION INTERMEDIATE
Overview
The crystal structure of porcine pancreatic elastase (PPE) complexed to carbobenzoxy-alanylisoleucine-boronic acid (ZAIB) is reported to 2.09-A resolution and refined to an R factor of 0.15. This is the first reported structural analysis of PPE with an isoleucine residu in the primary specificity pocket. The results include (1) marked displacement of the inhibitor out of the active site leading to (2) a close (2.2 A) direct contact between B (boron atom of the inhibitor) and N epsilon of His-57 and also (3) covalent bonding (1.5 A) to O gamma of Ser-195. A scheme for the mechanism of inhibition of PPE by ZAIB is proposed. A comparison with a peptidyl difluoromethyl ketone-PPE complex (Ki = 9.5 microns) is made to explain the strong inhibition of PPE by ZAIB (Ki = 0.3 micron). These results lead us to characterize this structure as a time- and space-averaged reaction intermediate, providing fresh insight into the cramped dimensions available in enzymatic catalyses.
About this Structure
5EST is a Single protein structure of sequence from [1] with and as ligands. Active as Pancreatic elastase, with EC number 3.4.21.36 Full crystallographic information is available from OCA.
Reference
Crystallographic analysis of the inhibition of porcine pancreatic elastase by a peptidyl boronic acid: structure of a reaction intermediate., Takahashi LH, Radhakrishnan R, Rosenfield RE Jr, Meyer EF Jr, Biochemistry. 1989 Sep 19;28(19):7610-7. PMID:2611205
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