1hkv

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{{STRUCTURE_1hkv| PDB=1hkv | SCENE= }}
{{STRUCTURE_1hkv| PDB=1hkv | SCENE= }}
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'''MYCOBACTERIUM DIAMINOPIMELATE DICARBOXYLASE (LYSA)'''
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===MYCOBACTERIUM DIAMINOPIMELATE DICARBOXYLASE (LYSA)===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12637582 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12637582}}
==About this Structure==
==About this Structure==
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[[Category: Plp]]
[[Category: Plp]]
[[Category: Tbsgc]]
[[Category: Tbsgc]]
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Revision as of 05:19, 1 July 2008

Image:1hkv.png

Template:STRUCTURE 1hkv

MYCOBACTERIUM DIAMINOPIMELATE DICARBOXYLASE (LYSA)

Template:ABSTRACT PUBMED 12637582

About this Structure

1HKV is a Single protein structure of sequence from Mycobacterium tuberculosis. 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

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