{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:22:06Z","timestamp":1790043726614,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,9,5]],"date-time":"2007-09-05T00:00:00Z","timestamp":1188950400000},"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":[[2008,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gaucher disease, the most prevalent lysosomal storage disorder, is principally caused by malfunction of the lysosomal enzyme glucocerebrosidase (GBA), a 497\u2010amino acid membrane glycoprotein that catalyzes the hydrolysis of glucosylceramide to ceramide and glucose in the presence of an essential 84\u2010residue activator peptide named saposin C (SapC). Knowledge of the GBA structure, a typical (\u03b2\/\u03b1)<jats:sub>8<\/jats:sub> TIM barrel, explains the effect of few mutations, directly affecting or located near the catalytic site. To identify new regions crucial for proper GBA functionality, we analyzed the interactions of the enzyme with a second (substrate) and a third (cofactor) partner. We build 3D docking models of the GBA\u2013SapC and the GBA\u2013ceramide interactions, by means of methodologies that integrate both evolutive and structural information. The GBA\u2013SapC docking model confirm the implication of three spatially closed regions of the GBA surface (TIM barrel\u2010helix 6 and helix 7, and the Ig\u2010like domain) in binding the SapC molecule. This model provides new basis to understand the pathogenicity of several mutations, such as the prevalent Leu444Pro, and the additive effect of Glu326Lys in the double mutant Glu326Lys\u2010Leu444Pro. Overall, 39 positions in which amino acid changes are known to cause Gaucher disease were localized in the GBA regions identified in this work. Our model is discussed in relation to the phenotype (pathogenic effect) of these mutations, as well as to the enzymatic activity of the recombinant proteins when available. Both data fully correlates with the proposed model, which will provide a new tool to better understand Gaucher disease and to design new therapy strategies. Proteins 2008. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.21554","type":"journal-article","created":{"date-parts":[[2007,9,5]],"date-time":"2007-09-05T21:47:35Z","timestamp":1189028855000},"page":"882-891","source":"Crossref","is-referenced-by-count":38,"title":["An evolutionary and structure\u2010based docking model for glucocerebrosidase\u2013saposin C and glucocerebrosidase\u2013substrate interactions\u2014Relevance for Gaucher disease"],"prefix":"10.1002","volume":"70","author":[{"given":"S\u00edlvia","family":"Atrian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"L\u00f3pez\u2010Vi\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulino","family":"G\u00f3mez\u2010Puertas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amparo","family":"Chab\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00efsa","family":"Vilageliu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Grinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,2]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03403534"},{"key":"e_1_2_6_4_2","series-title":"The 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