8CWP
X-ray crystal structure of NTHi Protein D bound to a putative glycerol moiety
Summary for 8CWP
| Entry DOI | 10.2210/pdb8cwp/pdb |
| Descriptor | Glycerophosphoryl diester phosphodiesterase, SODIUM ION, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | nthi, otitis media, outer membrane protein, phosphodiesterase, lipo-glycerophosphodiesterase, sn-glycero-3-phosphocholine, choline, sn-glycerol 3-phosphate, hydrolase |
| Biological source | Haemophilus influenzae |
| Total number of polymer chains | 1 |
| Total formula weight | 41393.95 |
| Authors | Jones, S.P.,Cook, K.H.,Holmquist, M.L.,Almekinder, L.,DeLaney, A.,Labbe, N.,Perdue, J.,Jackson, N.,Charles, R.,Pichichero, M.,Kaur, R.,Michel, L.,Gleghorn, M.L. (deposition date: 2022-05-19, release date: 2022-09-28, Last modification date: 2023-10-25) |
| Primary citation | Jones, S.P.,Cook, K.H.,Holmquist, M.L.,Almekinder, L.J.,Delaney, A.M.,Charles, R.,Labbe, N.,Perdue, J.,Jackson, N.,Pichichero, M.E.,Kaur, R.,Michel, L.V.,Gleghorn, M.L. Vaccine target and carrier molecule nontypeable Haemophilus influenzae protein D dimerizes like the close Escherichia coli GlpQ homolog but unlike other known homolog dimers. Proteins, 91:161-170, 2023 Cited by PubMed Abstract: We have determined the 1.8 Å 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. PubMed: 36065600DOI: 10.1002/prot.26418 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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