4IIP
Legionella pneumophila effector
Summary for 4IIP
| Entry DOI | 10.2210/pdb4iip/pdb |
| Related | 4IIK |
| Descriptor | Adenosine monophosphate-protein hydrolase SidD, GLYCEROL, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | beta sandwich, de-ampylation, rab1, legionella containing vacuole surface, hydrolase |
| Biological source | Legionella pneumophila |
| Cellular location | Host cytoplasm, host perinuclear region: Q5ZSQ2 |
| Total number of polymer chains | 1 |
| Total formula weight | 37022.05 |
| Authors | Tascon, I.,Chen, Y.,Neunuebel, M.R.,Rojas, A.L.,Machner, M.P.,Hierro, A. (deposition date: 2012-12-20, release date: 2013-06-19, Last modification date: 2024-03-20) |
| Primary citation | Chen, Y.,Tascon, I.,Neunuebel, M.R.,Pallara, C.,Brady, J.,Kinch, L.N.,Fernandez-Recio, J.,Rojas, A.L.,Machner, M.P.,Hierro, A. Structural Basis for Rab1 De-AMPylation by the Legionella pneumophila Effector SidD Plos Pathog., 9:e1003382-e1003382, 2013 Cited by PubMed Abstract: The covalent attachment of adenosine monophosphate (AMP) to proteins, a process called AMPylation (adenylylation), has recently emerged as a novel theme in microbial pathogenesis. Although several AMPylating enzymes have been characterized, the only known virulence protein with de-AMPylation activity is SidD from the human pathogen Legionella pneumophila. SidD de-AMPylates mammalian Rab1, a small GTPase involved in secretory vesicle transport, thereby targeting the host protein for inactivation. The molecular mechanisms underlying Rab1 recognition and de-AMPylation by SidD are unclear. Here, we report the crystal structure of the catalytic region of SidD at 1.6 Å resolution. The structure reveals a phosphatase-like fold with additional structural elements not present in generic PP2C-type phosphatases. The catalytic pocket contains a binuclear metal-binding site characteristic of hydrolytic metalloenzymes, with strong dependency on magnesium ions. Subsequent docking and molecular dynamics simulations between SidD and Rab1 revealed the interface contacts and the energetic contribution of key residues to the interaction. In conjunction with an extensive structure-based mutational analysis, we provide in vivo and in vitro evidence for a remarkable adaptation of SidD to its host cell target Rab1 which explains how this effector confers specificity to the reaction it catalyses. PubMed: 23696742DOI: 10.1371/journal.ppat.1003382 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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