5AHW

Crystal structure of universal stress protein MSMEG_3811 in complex with cAMP

5AHW の概要

• エントリーDOI: 10.2210/pdb5ahw/pdb
• 分子名称: UNIVERSAL STRESS PROTEIN, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: signaling protein, rv1636 homolog, usp type 1 homodimer, walker a-like motif, atp-binding motif
• 由来する生物種: MYCOBACTERIUM SMEGMATIS STR. MC2 155
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 95331.06

構造登録者

Adolph, R.S.,Kleinboelting, S.,Weyand, M.,Steegborn, C. (登録日: 2015-02-10, 公開日: 2015-04-01, 最終更新日: 2024-01-10)

主引用文献

Banerjee, A.,Adolph, R.S.,Gopalakrishnapai, J.,Kleinboelting, S.,Emmerich, C.,Steegborn, C.,Visweswariah, S.S.
A Universal Stress Protein (Usp) in Mycobacteria Binds Camp
J.Biol.Chem., 290:12731-, 2015

PubMed Abstract: Mycobacteria are endowed with rich and diverse machinery for the synthesis, utilization, and degradation of cAMP. The actions of cyclic nucleotides are generally mediated by binding of cAMP to conserved and well characterized cyclic nucleotide binding domains or structurally distinct cGMP-specific and -regulated cyclic nucleotide phosphodiesterase, adenylyl cyclase, and E. coli transcription factor FhlA (GAF) domain-containing proteins. Proteins with cyclic nucleotide binding and GAF domains can be identified in the genome of mycobacterial species, and some of them have been characterized. Here, we show that a significant fraction of intracellular cAMP is bound to protein in mycobacterial species, and by using affinity chromatography techniques, we identify specific universal stress proteins (USP) as abundantly expressed cAMP-binding proteins in slow growing as well as fast growing mycobacteria. We have characterized the biochemical and thermodynamic parameters for binding of cAMP, and we show that these USPs bind cAMP with a higher affinity than ATP, an established ligand for other USPs. We determined the structure of the USP MSMEG_3811 bound to cAMP, and we confirmed through structure-guided mutagenesis, the residues important for cAMP binding. This family of USPs is conserved in all mycobacteria, and we suggest that they serve as "sinks" for cAMP, making this second messenger available for downstream effectors as and when ATP levels are altered in the cell.

PubMed: 25802331
DOI: 10.1074/JBC.M115.644856

実験手法

X-RAY DIFFRACTION (2.15 Å)