5BU2

Structure of the C-terminal domain of lpg1496 from Legionella pneumophila in complex with nucleotide

Summary for 5BU2

• Entry DOI: 10.2210/pdb5bu2/pdb
• Related: 5BTX 5BTZ 5BU0 5BU1
• Descriptor: lpg1496, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE MONOPHOSPHATE, ... (5 entities in total)
• Functional Keywords: bacterial effector, nucleotide-binding, complex, structural genomics, montreal-kingston bacterial structural genomics initiative, bsgi, unknown function
• Biological source: Legionella pneumophila subsp. pneumophila ATCC 43290
• Total number of polymer chains: 4
• Total formula weight: 207117.23

Authors

Wong, K.,Kozlov, G.,Gehring, K.,Montreal-Kingston Bacterial Structural Genomics Initiative (BSGI) (deposition date: 2015-06-03, release date: 2015-08-26, Last modification date: 2023-09-27)

Primary citation

Wong, K.,Kozlov, G.,Zhang, Y.,Gehring, K.
Structure of the Legionella Effector, lpg1496, Suggests a Role in Nucleotide Metabolism.
J.Biol.Chem., 290:24727-24737, 2015

PubMed Abstract: Pathogenic Gram-negative bacteria use specialized secretion systems that translocate bacterial proteins, termed effectors, directly into host cells where they interact with host proteins and biochemical processes for the benefit of the pathogen. lpg1496 is a previously uncharacterized effector of Legionella pneumophila, the causative agent of Legionnaires disease. Here, we crystallized three nucleotide binding domains from lpg1496. The C-terminal domain, which is conserved among the SidE family of effectors, is formed of two largely α-helical lobes with a nucleotide binding cleft. A structural homology search has shown similarity to phosphodiesterases involved in cleavage of cyclic nucleotides. We have also crystallized a novel domain that occurs twice in the N-terminal half of the protein that we term the KLAMP domain due to the presence of homologous domains in bacterial histidine kinase-like ATP binding region-containing proteins and S-adenosylmethionine-dependent methyltransferase proteins. Both KLAMP structures are very similar but selectively bind 3',5'-cAMP and ADP. A co-crystal of the KLAMP1 domain with 3',5'-cAMP reveals the contribution of Tyr-61 and Tyr-69 that produces π-stacking interactions with the adenine ring of the nucleotide. Our study provides the first structural insights into two novel nucleotide binding domains associated with bacterial virulence.

PubMed: 26294765
DOI: 10.1074/jbc.M115.671263

Experimental method

X-RAY DIFFRACTION (2.11 Å)