2QZ8

Crystal structure of Mycobacterium tuberculosis Leucine response regulatory protein (LrpA)

2QZ8 の概要

• エントリーDOI: 10.2210/pdb2qz8/pdb
• 関連するPDBエントリー: 2QYD
• 分子名称: Probable transcriptional regulatory protein (2 entities in total)
• 機能のキーワード: leucine responsive regulatory protein, hth motif, global transcriptional regulator, structural genomics, tb structural genomics consortium, tbsgc, psi, protein structure initiative, dna-binding, transcription regulation, transcription
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 65781.97

構造登録者

Manchi, C.M.R.,Gokulan, K.,Ioerger, T.,Jacobs Jr., W.R.,Sacchettini, J.C.,TB Structural Genomics Consortium (TBSGC) (登録日: 2007-08-16, 公開日: 2007-11-06, 最終更新日: 2024-02-21)

主引用文献

Reddy, M.C.,Gokulan, K.,Jacobs, W.R.,Ioerger, T.R.,Sacchettini, J.C.
Crystal structure of Mycobacterium tuberculosis LrpA, a leucine-responsive global regulator associated with starvation response.
Protein Sci., 17:159-170, 2008

PubMed Abstract: The bacterial leucine-responsive regulatory protein (Lrp) is a global transcriptional regulator that controls the expression of many genes during starvation and the transition to stationary phase. The Mycobacterium tuberculosis gene Rv3291c encodes a 150-amino acid protein (designated here as Mtb LrpA) with homology with Escherichia coli Lrp. The crystal structure of the native form of Mtb LrpA was solved at 2.1 A. The Mtb LrpA structure shows an N-terminal DNA-binding domain with a helix-turn-helix (HTH) motif, and a C-terminal regulatory domain. In comparison to the complex of E. coli AsnC with asparagine, the effector-binding pocket (including loop 100-106) in LrpA appears to be largely preserved, with hydrophobic substitutions consistent with its specificity for leucine. The effector-binding pocket is formed at the interface between adjacent dimers, with an opening to the core of the octamer as in AsnC, and an additional substrate-access channel opening to the outer surface of the octamer. Using electrophoretic mobility shift assays, purified Mtb LrpA protein was shown to form a protein-DNA complex with the lat promoter, demonstrating that the lat operon is a direct target of LrpA. Using computational analysis, a putative motif is identified in this region that is also present upstream of other operons differentially regulated under starvation. This study provides insights into the potential role of LrpA as a global regulator in the transition of M. tuberculosis to a persistent state.

PubMed: 18042675
DOI: 10.1110/ps.073192208

実験手法

X-RAY DIFFRACTION (2.16 Å)