{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:04:03Z","timestamp":1772751843998,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have determined the 1.8\u00a0\u00c5 X\u2010ray crystal structure of nonlipidated (i.e., N\u2010terminally truncated) nontypeable <jats:italic>Haemophilus influenzae<\/jats:italic> (NTHi; <jats:italic>H<\/jats:italic>. <jats:italic>influenzae<\/jats:italic>) protein D. Protein D exists on outer membranes of <jats:italic>H. influenzae<\/jats:italic> 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\u2122. NTHi protein D shares high sequence and structural identify to the <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>) <jats:italic>glpQ<\/jats:italic> gene product (GlpQ). <jats:italic>E. coli<\/jats:italic> 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 <jats:italic>E. coli<\/jats:italic> GlpQ with other homologous homodimers and monomers shows that the <jats:italic>E. coli<\/jats:italic> and NTHi homodimer interfaces are distinct. Despite this distinction, NTHi protein D and <jats:italic>E. coli<\/jats:italic> GlpQ possess a triose\u2010phosphate 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.<\/jats:p>","DOI":"10.1002\/prot.26418","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T07:20:03Z","timestamp":1662448803000},"page":"161-170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vaccine target and carrier molecule nontypeable <i>Haemophilus influenzae<\/i> protein D dimerizes like the close <i>Escherichia coli<\/i><scp>GlpQ<\/scp> homolog but unlike other known homolog dimers"],"prefix":"10.1002","volume":"91","author":[{"given":"Seth P.","family":"Jones","sequence":"first","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  Rochester New York 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