The crystal structure of Methanococcus jannaschii shikimate 5-dehydrogenase (MjSDH) bound to the cofactor nicotinamide adenine dinucleotide phosphate (NADP) has been determined at 2.35 A resolution. Shikimate 5-dehydrogenase (SDH) is responsible for NADP-dependent catalysis of the fourth step in shikimate biosynthesis, which is essential for aromatic amino acid metabolism in bacteria, microbial eukaryotes, and plants. The structure of MjSDH is a compact alpha/beta sandwich with two distinct domains, responsible for binding substrate and the NADP cofactor, respectively. A phylogenetically conserved deep cleft on the protein surface corresponds to the enzyme active site. The structure reveals a topologically new domain fold within the N-terminal segment of the polypeptide chain, which binds substrate and supports dimerization. Insights gained from homology modeling and sequence/structure comparisons suggest that the SDHs represent a unique class of dehydrogenases. The structure provides a framework for further investigation to discover and develop novel inhibitors targeting this essential enzyme.
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|---|---|
| rdf:type | |
| rdfs:comment |
The crystal structure of Methanococcus jannaschii shikimate 5-dehydrogenase (MjSDH) bound to the cofactor nicotinamide adenine dinucleotide phosphate (NADP) has been determined at 2.35 A resolution. Shikimate 5-dehydrogenase (SDH) is responsible for NADP-dependent catalysis of the fourth step in shikimate biosynthesis, which is essential for aromatic amino acid metabolism in bacteria, microbial eukaryotes, and plants. The structure of MjSDH is a compact alpha/beta sandwich with two distinct domains, responsible for binding substrate and the NADP cofactor, respectively. A phylogenetically conserved deep cleft on the protein surface corresponds to the enzyme active site. The structure reveals a topologically new domain fold within the N-terminal segment of the polypeptide chain, which binds substrate and supports dimerization. Insights gained from homology modeling and sequence/structure comparisons suggest that the SDHs represent a unique class of dehydrogenases. The structure provides a framework for further investigation to discover and develop novel inhibitors targeting this essential enzyme.
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| skos:exactMatch | |
| uniprot:name |
Structure
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| uniprot:author |
Burley S.K.,
Padyana A.K.
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| uniprot:date |
2003
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| uniprot:pages |
1005-1013
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| uniprot:title |
Crystal structure of shikimate 5-dehydrogenase (SDH) bound to NADP: insights into function and evolution.
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| uniprot:volume |
11
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| dc-term:identifier |
doi:10.1016/S0969-2126(03)00159-X
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