{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:20:29Z","timestamp":1785331229482,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,12,9]],"date-time":"2002-12-09T00:00:00Z","timestamp":1039392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Esherichia coli,<\/jats:italic> the most common gram\u2010negative bacteria, can penetrate the brain microvascular endothelial cells (BMECs) during the neonatal period to cause meningitis with significant morbidity and mortality. Experimental studies have shown that outer\u2010membrane protein A (OmpA) of <jats:italic>E. coli<\/jats:italic> plays a key role in the initial steps of the invasion process by binding to specific sugar moieties present on the glycoproteins of BMEC. These experiments also show that polymers of chitobiose (GlcNAc\u03b21\u20104GlcNAc) block the invasion, while epitopes substituted with the <jats:sc>L<\/jats:sc>\u2010fucosyl group do not. We used HierDock computational technique that consists of a hierarchy of coarse grain docking method with molecular dynamics (MD) to predict the binding sites and energies of interactions of GlcNAc\u03b21\u20104GlcNAc and other sugars with OmpA. The results suggest two important binding sites for the interaction of carbohydrate epitopes of BMEC glycoproteins to OmpA. We identify one site as the binding pocket for chitobiose (GlcNAc\u03b21\u20104GlcNAc<jats:styled-content>)<\/jats:styled-content> in OmpA, while the second region (including loops 1 and 2) may be important for recognition of specific sugars. We find that the site involving loops 1 and 2 has relative binding energies that correlate well with experimental observations. This theoretical study elucidates the interaction sites of chitobiose with OmpA and the binding site predictions made in this article are testable either by mutation studies or invasion assays. These results can be further extended in suggesting possible peptide antagonists and drug design for therapeutic strategies. Proteins 2003;50:213\u2013221. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.10257","type":"journal-article","created":{"date-parts":[[2002,12,17]],"date-time":"2002-12-17T14:13:01Z","timestamp":1040134381000},"page":"213-221","source":"Crossref","is-referenced-by-count":32,"title":["Interaction of <i>e. coli<\/i> outer\u2010membrane protein A with sugars on the receptors of the brain microvascular endothelial cells"],"prefix":"10.1002","volume":"50","author":[{"given":"Deepshikha","family":"Datta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagarajan","family":"Vaidehi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wely B.","family":"Floriano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang S.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nemani V.","family":"Prasadarao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William A.","family":"Goddard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,12,9]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199011000-00009"},{"key":"e_1_2_7_3_2","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1542\/peds.78.5.959","article-title":"Report of the Task Force on Diagnosis and Management of Meningitis","volume":"78","author":"Klein JO","year":"1986","journal-title":"Pediatrics"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)83480-8"},{"key":"e_1_2_7_5_2","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1128\/iai.64.1.146-153.1996","article-title":"Outer membrane protein A of Escherichia coli contributes to invasion of brain microvascular endothelial cells","volume":"64","author":"Prasadarao NV","year":"1996","journal-title":"Infect Immunol"},{"key":"e_1_2_7_6_2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1128\/iai.64.1.154-160.1996","article-title":"Endothelial cell GlcNAc beta 1\u20104GlcNAc epitopes for outer membrane protein A enhance traversal of Escherichia coli across the blood\u2010brain barrier","volume":"64","author":"Prasadarao NV","year":"1996","journal-title":"Infect Immunol"},{"key":"e_1_2_7_7_2","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1128\/iai.65.7.2852-2860.1997","article-title":"Identification and characterization of S fimbria\u2010binding sialoglycoproteins on brain microvascular endothelial cells","volume":"65","author":"Prasadarao NV","year":"1997","journal-title":"Infect Immunol"},{"key":"e_1_2_7_8_2","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1128\/IAI.67.11.5775-5783.1999","article-title":"Outer membrane protein A\u2010promoted actin condensation of brain microvascular endothelial cells is required for Escherichia coli invasion","volume":"67","author":"Prasadarao NV","year":"1999","journal-title":"Infect Immunol"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1674624"},{"key":"e_1_2_7_10_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1042\/bj2700197","article-title":"Receptor\u2010mediated endocytosis of ovalbumin by two carbohydrate\u2010specific receptors in rat liver cells. 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