2gz2
From Proteopedia
(New page: 200px<br /><applet load="2gz2" size="350" color="white" frame="true" align="right" spinBox="true" caption="2gz2, resolution 2.100Å" /> '''Structure of Aspart...) |
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caption="2gz2, resolution 2.100Å" /> | caption="2gz2, resolution 2.100Å" /> | ||
'''Structure of Aspartate Semialdehyde Dehydrogenase (ASADH) from Streptococcus pneumoniae complexed with 2',5'-ADP'''<br /> | '''Structure of Aspartate Semialdehyde Dehydrogenase (ASADH) from Streptococcus pneumoniae complexed with 2',5'-ADP'''<br /> | ||
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| + | ==Overview== | ||
| + | Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes a critical, branch point transformation in amino acid bio-synthesis. The products of, the aspartate pathway are essential in microorganisms, and this entire, pathway is absent in mammals, making this enzyme an attractive target for, antibiotic development. The first structure of an ASADH from a, Gram-positive bacterium, Streptococcus pneumoniae, has now been, determined. The overall structure of the apoenzyme has a similar fold to, those of the Gram-negative and archaeal ASADHs but contains some, interesting structural variations that can be exploited for inhibitor, design. Binding of the coenzyme NADP, as well as a truncated nucleotide, analogue, into an alternative conformation from that observed in, Gram-negative ASADHs causes an enzyme domain closure that precedes, catalysis. The covalent acyl-enzyme intermediate was trapped by soaking, the substrate into crystals of the coenzyme complex, and the structure of, this elusive intermediate provides detailed insights into the catalytic, mechanism. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2GZ2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae] with <scene name='pdbligand=A2P:'>A2P</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=2GZ2 OCA]. | + | 2GZ2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae] with <scene name='pdbligand=A2P:'>A2P</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Known structural/functional Sites: <scene name='pdbsite=AC1:A2p+Binding+Site+For+Residue+B+501'>AC1</scene> and <scene name='pdbsite=AC2:A2p+Binding+Site+For+Residue+A+502'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GZ2 OCA]. |
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| + | ==Reference== | ||
| + | Examination of key intermediates in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase from a gram-positive infectious bacteria., Faehnle CR, Le Coq J, Liu X, Viola RE, J Biol Chem. 2006 Oct 13;281(41):31031-40. Epub 2006 Aug 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16895909 16895909] | ||
[[Category: Aspartate-semialdehyde dehydrogenase]] | [[Category: Aspartate-semialdehyde dehydrogenase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: aspartate pathway]] | [[Category: aspartate pathway]] | ||
[[Category: dehydrogenase]] | [[Category: dehydrogenase]] | ||
| + | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:17:19 2008'' |
Revision as of 06:17, 13 February 2008
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Structure of Aspartate Semialdehyde Dehydrogenase (ASADH) from Streptococcus pneumoniae complexed with 2',5'-ADP
Overview
Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes a critical, branch point transformation in amino acid bio-synthesis. The products of, the aspartate pathway are essential in microorganisms, and this entire, pathway is absent in mammals, making this enzyme an attractive target for, antibiotic development. The first structure of an ASADH from a, Gram-positive bacterium, Streptococcus pneumoniae, has now been, determined. The overall structure of the apoenzyme has a similar fold to, those of the Gram-negative and archaeal ASADHs but contains some, interesting structural variations that can be exploited for inhibitor, design. Binding of the coenzyme NADP, as well as a truncated nucleotide, analogue, into an alternative conformation from that observed in, Gram-negative ASADHs causes an enzyme domain closure that precedes, catalysis. The covalent acyl-enzyme intermediate was trapped by soaking, the substrate into crystals of the coenzyme complex, and the structure of, this elusive intermediate provides detailed insights into the catalytic, mechanism.
About this Structure
2GZ2 is a Single protein structure of sequence from Streptococcus pneumoniae with as ligand. Active as Aspartate-semialdehyde dehydrogenase, with EC number 1.2.1.11 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Examination of key intermediates in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase from a gram-positive infectious bacteria., Faehnle CR, Le Coq J, Liu X, Viola RE, J Biol Chem. 2006 Oct 13;281(41):31031-40. Epub 2006 Aug 8. PMID:16895909
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