8cwp

X-ray crystal structure of NTHi Protein D bound to a putative glycerol moiety

spinqualitylabelsall models 8cwp, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8cwp is a 1 chain structure with sequence from Haemophilus influenzae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A8D4QYM6_HAEIF Publication Abstract from PubMed We have determined the 1.8 A X-ray crystal structure of nonlipidated (i.e., N-terminally truncated) nontypeable Haemophilus influenzae (NTHi; H. influenzae) protein D. Protein D exists on outer membranes of H. influenzae strains and acts as a virulence factor that helps invade human cells. Protein D is a proven successful antigen in animal models to treat obstructive pulmonary disease (COPD) and otitis media (OM), and when conjugated to polysaccharides also has been used as a carrier molecule for human vaccines, for example in GlaxoSmithKline Synflorix. NTHi protein D shares high sequence and structural identify to the Escherichia coli (E. coli) glpQ gene product (GlpQ). E. coli GlpQ is a glycerophosphodiester phosphodiesterase (GDPD) with a known dimeric structure in the Protein Structural Database, albeit without an associated publication. We show here that both structures exhibit similar homodimer organization despite slightly different crystal lattices. Additionally, we have observed both the presence of weak dimerization and the lack of dimerization in solution during size exclusion chromatography (SEC) experiments yet have distinctly observed dimerization in native mass spectrometry analyses. Comparison of NTHi protein D and E. coli GlpQ with other homologous homodimers and monomers shows that the E. coli and NTHi homodimer interfaces are distinct. Despite this distinction, NTHi protein D and E. coli GlpQ possess a triose-phosphate isomerase (TIM) barrel domain seen in many of the other homologs. The active site of NTHi protein D is located near the center of this TIM barrel. A putative glycerol moiety was modeled in two different conformations (occupancies) in the active site of our NTHi protein D structure and we compared this to ligands modeled in homologous structures. Our structural analysis should aid in future efforts to determine structures of protein D bound to substrates, analog intermediates, and products, to fully appreciate this reaction scheme and aiding in future inhibitor design. Vaccine target and carrier molecule nontypeable Haemophilus influenzae protein D dimerizes like the close Escherichia coli GlpQ homolog but unlike other known homolog dimers.,Jones SP, Cook KH, Holmquist ML, Almekinder LJ, Delaney AM, Charles R, Labbe N, Perdue J, Jackson N, Pichichero ME, Kaur R, Michel LV, Gleghorn ML Proteins. 2022 Sep 6. doi: 10.1002/prot.26418. PMID:36065600 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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