2A8X

Crystal Structure of Lipoamide Dehydrogenase from Mycobacterium tuberculosis

Summary for 2A8X

• Entry DOI: 10.2210/pdb2a8x/pdb
• Descriptor: Dihydrolipoyl dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: lipoamide dehydrogenase; pyruvate dehydrogenase; alpha keto acid dehydrogenase, oxidoreductase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 100931.60

Authors

Rajashankar, K.R.,Bryk, R.,Kniewel, R.,Buglino, J.A.,Nathan, C.F.,Lima, C.D. (deposition date: 2005-07-10, release date: 2005-08-16, Last modification date: 2024-04-03)

Primary citation

Rajashankar, K.R.,Bryk, R.,Kniewel, R.,Buglino, J.A.,Nathan, C.F.,Lima, C.D.
Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis
J.Biol.Chem., 280:33977-33983, 2005

PubMed Abstract: We report the 2.4 A crystal structure for lipoamide dehydrogenase encoded by lpdC from Mycobacterium tuberculosis. Based on the Lpd structure and sequence alignment between bacterial and eukaryotic Lpd sequences, we generated single point mutations in Lpd and assayed the resulting proteins for their ability to catalyze lipoamide reduction/oxidation alone and in complex with other proteins that participate in pyruvate dehydrogenase and peroxidase activities. The results suggest that amino acid residues conserved in mycobacterial species but not conserved in eukaryotic Lpd family members modulate either or both activities and include Arg-93, His-98, Lys-103, and His-386. In addition, Arg-93 and His-386 are involved in forming both "open" and "closed" active site conformations, suggesting that these residues play a role in dynamically regulating Lpd function. Taken together, these data suggest protein surfaces that should be considered while developing strategies for inhibiting this enzyme.

PubMed: 16093239
DOI: 10.1074/jbc.M507466200

Experimental method

X-RAY DIFFRACTION (2.4 Å)