1nwc
From Proteopedia
(New page: 200px<br /><applet load="1nwc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nwc, resolution 2.04Å" /> '''Crystal Structure of...) |
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| - | [[Image:1nwc.gif|left|200px]]<br /><applet load="1nwc" size=" | + | [[Image:1nwc.gif|left|200px]]<br /><applet load="1nwc" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1nwc, resolution 2.04Å" /> | caption="1nwc, resolution 2.04Å" /> | ||
'''Crystal Structure of Aspartate-Semialdehyde Dehydrogenase from Haemophilus influenzae'''<br /> | '''Crystal Structure of Aspartate-Semialdehyde Dehydrogenase from Haemophilus influenzae'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structural analysis of an enzymatic reaction intermediate affords a | + | The structural analysis of an enzymatic reaction intermediate affords a unique opportunity to study a catalytic mechanism in extraordinary detail. Here we present the structure of a tetrahedral intermediate in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase (ASADH) from Haemophilus influenzae at 2.0-A resolution. ASADH is not found in humans, yet its catalytic activity is required for the biosynthesis of essential amino acids in plants and microorganisms. Diaminopimelic acid, also formed by this enzymatic pathway, is an integral component of bacterial cell walls, thus making ASADH an attractive target for the development of new antibiotics. This enzyme is able to capture the substrates aspartate-beta-semialdehyde and phosphate as an active complex that does not complete the catalytic cycle in the absence of NADP. A distinctive binding pocket in which the hemithioacetal oxygen of the bound substrate is stabilized by interaction with a backbone amide group dictates the R stereochemistry of the tetrahedral intermediate. This pocket, reminiscent of the oxyanion hole found in serine proteases, is completed through hydrogen bonding to the bound phosphate substrate. |
==About this Structure== | ==About this Structure== | ||
| - | 1NWC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae]. Active as [http://en.wikipedia.org/wiki/Aspartate-semialdehyde_dehydrogenase Aspartate-semialdehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.11 1.2.1.11] Full crystallographic information is available from [http:// | + | 1NWC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae]. Active as [http://en.wikipedia.org/wiki/Aspartate-semialdehyde_dehydrogenase Aspartate-semialdehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.11 1.2.1.11] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NWC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Blanco, J.]] | [[Category: Blanco, J.]] | ||
| - | [[Category: Moore, R | + | [[Category: Moore, R A.]] |
| - | [[Category: Viola, R | + | [[Category: Viola, R E.]] |
[[Category: aspartate-semialdehyde dehydrogenase]] | [[Category: aspartate-semialdehyde dehydrogenase]] | ||
[[Category: enzyme]] | [[Category: enzyme]] | ||
[[Category: haemophilus influenzae]] | [[Category: haemophilus influenzae]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:10:49 2008'' |
Revision as of 12:10, 21 February 2008
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Crystal Structure of Aspartate-Semialdehyde Dehydrogenase from Haemophilus influenzae
Overview
The structural analysis of an enzymatic reaction intermediate affords a unique opportunity to study a catalytic mechanism in extraordinary detail. Here we present the structure of a tetrahedral intermediate in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase (ASADH) from Haemophilus influenzae at 2.0-A resolution. ASADH is not found in humans, yet its catalytic activity is required for the biosynthesis of essential amino acids in plants and microorganisms. Diaminopimelic acid, also formed by this enzymatic pathway, is an integral component of bacterial cell walls, thus making ASADH an attractive target for the development of new antibiotics. This enzyme is able to capture the substrates aspartate-beta-semialdehyde and phosphate as an active complex that does not complete the catalytic cycle in the absence of NADP. A distinctive binding pocket in which the hemithioacetal oxygen of the bound substrate is stabilized by interaction with a backbone amide group dictates the R stereochemistry of the tetrahedral intermediate. This pocket, reminiscent of the oxyanion hole found in serine proteases, is completed through hydrogen bonding to the bound phosphate substrate.
About this Structure
1NWC is a Single protein structure of sequence from Haemophilus influenzae. Active as Aspartate-semialdehyde dehydrogenase, with EC number 1.2.1.11 Full crystallographic information is available from OCA.
Reference
Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase., Blanco J, Moore RA, Viola RE, Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12613-7. Epub 2003 Oct 14. PMID:14559965
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