1hkv
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The Mycobacterium tuberculosis lysA gene encodes the enzyme | + | The Mycobacterium tuberculosis lysA gene encodes the enzyme meso-diaminopimelate decarboxylase (DAPDC), a pyridoxal-5'-phosphate (PLP)-dependent enzyme. The enzyme catalyzes the final step in the lysine biosynthetic pathway converting meso-diaminopimelic acid (DAP) to l-lysine. The lysA gene of M. tuberculosis H37Rv has been established as essential for bacterial survival in immunocompromised mice, demonstrating that de novo biosynthesis of lysine is essential for in vivo viability. Drugs targeted against DAPDC could be efficient anti-tuberculosis drugs, and the three-dimensional structure of DAPDC from M. tuberculosis complexed with reaction product lysine and the ternary complex with PLP and lysine in the active site has been determined. The first structure of a DAPDC confirms its classification as a fold type III PLP-dependent enzyme. The structure shows a stable 2-fold dimer in head-to-tail arrangement of a triose-phosphate isomerase (TIM) barrel-like alpha/beta domain and a C-terminal beta sheet domain, similar to the ornithine decarboxylase (ODC) fold family. PLP is covalently bound via an internal aldimine, and residues from both domains and both subunits contribute to the binding pocket. Comparison of the structure with eukaryotic ODCs, in particular with a di-fluoromethyl ornithine (DMFO)-bound ODC from Trypanosoma bruceii, indicates that corresponding DAP-analogues might be potential inhibitors for mycobacterial DAPDCs. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Gokulan, K.]] | [[Category: Gokulan, K.]] | ||
| - | [[Category: Junior, M | + | [[Category: Junior, M S.Pavelka.]] |
| - | [[Category: Junior, W | + | [[Category: Junior, W R.Jacobs.]] |
[[Category: Rupp, B.]] | [[Category: Rupp, B.]] | ||
| - | [[Category: Sacchettini, J | + | [[Category: Sacchettini, J C.]] |
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: LYS]] | [[Category: LYS]] | ||
[[Category: PLP]] | [[Category: PLP]] | ||
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[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''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 13:02:18 2008'' |
Revision as of 11:02, 21 February 2008
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MYCOBACTERIUM DIAMINOPIMELATE DICARBOXYLASE (LYSA)
Overview
The Mycobacterium tuberculosis lysA gene encodes the enzyme meso-diaminopimelate decarboxylase (DAPDC), a pyridoxal-5'-phosphate (PLP)-dependent enzyme. The enzyme catalyzes the final step in the lysine biosynthetic pathway converting meso-diaminopimelic acid (DAP) to l-lysine. The lysA gene of M. tuberculosis H37Rv has been established as essential for bacterial survival in immunocompromised mice, demonstrating that de novo biosynthesis of lysine is essential for in vivo viability. Drugs targeted against DAPDC could be efficient anti-tuberculosis drugs, and the three-dimensional structure of DAPDC from M. tuberculosis complexed with reaction product lysine and the ternary complex with PLP and lysine in the active site has been determined. The first structure of a DAPDC confirms its classification as a fold type III PLP-dependent enzyme. The structure shows a stable 2-fold dimer in head-to-tail arrangement of a triose-phosphate isomerase (TIM) barrel-like alpha/beta domain and a C-terminal beta sheet domain, similar to the ornithine decarboxylase (ODC) fold family. PLP is covalently bound via an internal aldimine, and residues from both domains and both subunits contribute to the binding pocket. Comparison of the structure with eukaryotic ODCs, in particular with a di-fluoromethyl ornithine (DMFO)-bound ODC from Trypanosoma bruceii, indicates that corresponding DAP-analogues might be potential inhibitors for mycobacterial DAPDCs.
About this Structure
1HKV is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Active as Diaminopimelate decarboxylase, with EC number 4.1.1.20 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis., Gokulan K, Rupp B, Pavelka MS Jr, Jacobs WR Jr, Sacchettini JC, J Biol Chem. 2003 May 16;278(20):18588-96. Epub 2003 Mar 10. PMID:12637582
Page seeded by OCA on Thu Feb 21 13:02:18 2008
Categories: Diaminopimelate decarboxylase | Mycobacterium tuberculosis | Single protein | Gokulan, K. | Junior, M S.Pavelka. | Junior, W R.Jacobs. | Rupp, B. | Sacchettini, J C. | TBSGC, TB Structural Genomics Consortium. | LYS | PLP | Dapdc | Decarboxylase | Diaminopimelate | Lyase | Lysine pathway | Lysine synthetic pathway | Mycbacterium tuberculosis | Plp | Protein structure initiative | Psi | Pyridoxal phosphate | Tb | Tb structural genomics consortium | Tbsgc
