2gz1
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes a critical | + | 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== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Streptococcus pneumoniae]] | [[Category: Streptococcus pneumoniae]] | ||
| - | [[Category: Coq, J | + | [[Category: Coq, J Le.]] |
| - | [[Category: Faehnle, C | + | [[Category: Faehnle, C R.]] |
[[Category: Liu, X.]] | [[Category: Liu, X.]] | ||
| - | [[Category: Viola, R | + | [[Category: Viola, R E.]] |
[[Category: NAP]] | [[Category: NAP]] | ||
[[Category: aspartate pathway]] | [[Category: aspartate pathway]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''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 17:36:31 2008'' |
Revision as of 15:36, 21 February 2008
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Structure of Aspartate Semialdehyde Dehydrogenase (ASADH) from Streptococcus pneumoniae complexed with NADP
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
2GZ1 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
Page seeded by OCA on Thu Feb 21 17:36:31 2008
