1btw
From Proteopedia
(New page: 200px<br /><applet load="1btw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1btw, resolution 1.7Å" /> '''EPISELECTION: NOVEL K...) |
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| - | [[Image:1btw.gif|left|200px]]<br /><applet load="1btw" size=" | + | [[Image:1btw.gif|left|200px]]<br /><applet load="1btw" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1btw, resolution 1.7Å" /> | caption="1btw, resolution 1.7Å" /> | ||
'''EPISELECTION: NOVEL KI ~NANOMOLAR INHIBITORS OF SERINE PROTEASES SELECTED BY BINDING OR CHEMISTRY ON AN ENZYME SURFACE'''<br /> | '''EPISELECTION: NOVEL KI ~NANOMOLAR INHIBITORS OF SERINE PROTEASES SELECTED BY BINDING OR CHEMISTRY ON AN ENZYME SURFACE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A novel class of mechanism-based inhibitors of the serine proteases is | + | A novel class of mechanism-based inhibitors of the serine proteases is developed using epitaxial selection. Tripeptide boronates esterified by an alcohol or alcohols at the boron retain the tight binding to trypsin-like enzymes associated with transition-state analogs and incorporate additional groups that can be utilized for selectivity between proteases. Formed by reaction of a series of alcohols with the inhibitor boronate oxygen(s), the most structurally compatible alcohol-derivatized inhibitors are either selected by binding to the enzyme (epitaxial selection) or assembled by epitaxial reaction on the enzyme surface. Mass spectrometry of the derivatized boronates and X-ray crystallography of the complexes identify the chemical structures and the three-dimensional interactions of inhibitors generated. This scheme also engineers novel, potent (Ki approximately 7 nM), and more specific inhibitors of individual serine proteases, by derivitizations of compounds obtained by epitaxial selection. |
==About this Structure== | ==About this Structure== | ||
| - | 1BTW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with CA and PDO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http:// | + | 1BTW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=PDO:'>PDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BTW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Trypsin]] | [[Category: Trypsin]] | ||
[[Category: Finer-Moore, J.]] | [[Category: Finer-Moore, J.]] | ||
| - | [[Category: Katz, B | + | [[Category: Katz, B A.]] |
| - | [[Category: Stroud, R | + | [[Category: Stroud, R M.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: PDO]] | [[Category: PDO]] | ||
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[[Category: tripeptideboronate 1]] | [[Category: tripeptideboronate 1]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:59:04 2008'' |
Revision as of 09:59, 21 February 2008
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EPISELECTION: NOVEL KI ~NANOMOLAR INHIBITORS OF SERINE PROTEASES SELECTED BY BINDING OR CHEMISTRY ON AN ENZYME SURFACE
Overview
A novel class of mechanism-based inhibitors of the serine proteases is developed using epitaxial selection. Tripeptide boronates esterified by an alcohol or alcohols at the boron retain the tight binding to trypsin-like enzymes associated with transition-state analogs and incorporate additional groups that can be utilized for selectivity between proteases. Formed by reaction of a series of alcohols with the inhibitor boronate oxygen(s), the most structurally compatible alcohol-derivatized inhibitors are either selected by binding to the enzyme (epitaxial selection) or assembled by epitaxial reaction on the enzyme surface. Mass spectrometry of the derivatized boronates and X-ray crystallography of the complexes identify the chemical structures and the three-dimensional interactions of inhibitors generated. This scheme also engineers novel, potent (Ki approximately 7 nM), and more specific inhibitors of individual serine proteases, by derivitizations of compounds obtained by epitaxial selection.
About this Structure
1BTW is a Single protein structure of sequence from Bos taurus with and as ligands. Active as Trypsin, with EC number 3.4.21.4 Full crystallographic information is available from OCA.
Reference
Episelection: novel Ki approximately nanomolar inhibitors of serine proteases selected by binding or chemistry on an enzyme surface., Katz BA, Finer-Moore J, Mortezaei R, Rich DH, Stroud RM, Biochemistry. 1995 Jul 4;34(26):8264-80. PMID:7599119
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