Cooperativity of catalytic and lectin-like domain of Trypanosoma congolense trans-sialidase modulates its catalytic activity
Trans-sialidases (TS) represent a multi-gene family of unusual enzymes, which catalyse the transfer of terminal sialic acids (Sia) from sialoglycoconjugates to terminal galactose or N-acetylgalactosamine residues of oligosaccharides without the requirement of CMP-Neu5Ac, the activated Sia used by ty...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2022-02, Vol.16 (2), p.e0009585 |
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| description | Trans-sialidases (TS) represent a multi-gene family of unusual enzymes, which catalyse the transfer of terminal sialic acids (Sia) from sialoglycoconjugates to terminal galactose or N-acetylgalactosamine residues of oligosaccharides without the requirement of CMP-Neu5Ac, the activated Sia used by typical sialyltransferases. Enzymes comprise a N-terminal catalytic domain (CD) followed by a lectin-like domain (LD). Most work on trypanosomal TS has been done on enzymatic activities focusing on the CD of TS from Trypanosoma cruzi (causing Chagas disease in Latin America), subspecies of Trypanosoma brucei, (causing human sleeping sickness in Africa) and Trypanosoma congolense (causing African Animal Trypanosomosis in livestock). Previously, we demonstrated that T. congolense TS (TconTS)-LD binds to several carbohydrates, such as 1,4-β-mannotriose. In this study we investigated the influence of TconTS3-LD on Sia transfer efficiency of TconTS1a-CD by swapping domains. in silico analysis on structure models of TconTS enzymes revealed the potential of domain swaps between TconTS1a and TconTS3 without structural disruptions of the enzymes overall topologies. Recombinant domain swapped TconTS1a/TS3 showed clear Sia transfer activity, when using fetuin and lactose as Sia donor and acceptor substrates, respectively. While Sia transfer activity remained unchanged from the level of TconTS1a, hydrolytic release of free Neu5Ac as a side product was suppressed resulting in increased transfer efficiency. Presence of 1,4-β-mannotriose during TS reactions modulates enzyme activities enhancing transfer efficiency possibly due to occupation of the binding site in TconTS1a-LD. Interestingly this effect was in the same range as that observed when swapping TconTS1a-CD and TconTS3-LD. In summary, this study demonstrate the proof-of-principle for swapping CDs and LDs of TconTS and that TconTS3-LD influences enzymatic activity of TconTS1a-CD providing evidence that LDs play pivotal roles in modulating activities and biological functions of TconTS and possibly other TS. |
| doi_str_mv | 10.1371/journal.pntd.0009585 |
| format | Article |
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Enzymes comprise a N-terminal catalytic domain (CD) followed by a lectin-like domain (LD). Most work on trypanosomal TS has been done on enzymatic activities focusing on the CD of TS from Trypanosoma cruzi (causing Chagas disease in Latin America), subspecies of Trypanosoma brucei, (causing human sleeping sickness in Africa) and Trypanosoma congolense (causing African Animal Trypanosomosis in livestock). Previously, we demonstrated that T. congolense TS (TconTS)-LD binds to several carbohydrates, such as 1,4-β-mannotriose. In this study we investigated the influence of TconTS3-LD on Sia transfer efficiency of TconTS1a-CD by swapping domains. in silico analysis on structure models of TconTS enzymes revealed the potential of domain swaps between TconTS1a and TconTS3 without structural disruptions of the enzymes overall topologies. Recombinant domain swapped TconTS1a/TS3 showed clear Sia transfer activity, when using fetuin and lactose as Sia donor and acceptor substrates, respectively. While Sia transfer activity remained unchanged from the level of TconTS1a, hydrolytic release of free Neu5Ac as a side product was suppressed resulting in increased transfer efficiency. Presence of 1,4-β-mannotriose during TS reactions modulates enzyme activities enhancing transfer efficiency possibly due to occupation of the binding site in TconTS1a-LD. Interestingly this effect was in the same range as that observed when swapping TconTS1a-CD and TconTS3-LD. In summary, this study demonstrate the proof-of-principle for swapping CDs and LDs of TconTS and that TconTS3-LD influences enzymatic activity of TconTS1a-CD providing evidence that LDs play pivotal roles in modulating activities and biological functions of TconTS and possibly other TS.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0009585</identifier><identifier>PMID: 35130274</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetylgalactosamine - metabolism ; African trypanosomiasis ; Amino acids ; Binding Sites ; Biology and Life Sciences ; Carbohydrates ; Catalysis ; Catalytic activity ; Chagas disease ; Chemical properties ; Domains ; Efficiency ; Enzymatic activity ; Enzymatic analysis ; Enzyme activity ; Enzymes ; Galactose ; Galactose - metabolism ; Glycoproteins ; Glycoproteins - chemistry ; Glycoproteins - genetics ; Glycoproteins - metabolism ; Lactose ; Ligands ; Livestock ; Methods ; N-Acetylgalactosamine ; Neuraminidase - chemistry ; Neuraminidase - genetics ; Neuraminidase - metabolism ; Oligosaccharides ; Oligosaccharides - metabolism ; Parasites ; Physical Sciences ; Proteins ; Protozoan Proteins - chemistry ; Protozoan Proteins - genetics ; Protozoan Proteins - metabolism ; Recombinants ; Research and Analysis Methods ; Sialic acids ; Sialic Acids - metabolism ; Substrates ; Topology ; trans-Sialidase ; Tropical diseases ; Trypanosoma ; Trypanosoma congolense ; Trypanosoma congolense - chemistry ; Trypanosoma congolense - enzymology ; Trypanosoma congolense - genetics ; Varieties ; Vector-borne diseases</subject><ispartof>PLoS neglected tropical diseases, 2022-02, Vol.16 (2), p.e0009585</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Waespy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Waespy et al 2022 Waespy et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-aff1f51078bcb6f3ee6531d23693f3630c71ab80d28afd223b888930da09bee3</citedby><cites>FETCH-LOGICAL-c624t-aff1f51078bcb6f3ee6531d23693f3630c71ab80d28afd223b888930da09bee3</cites><orcidid>0000-0003-2757-0786 ; 0000-0003-0039-5770 ; 0000-0002-9341-8187 ; 0000-0001-5277-9421 ; 0000-0002-2366-0082 ; 0000-0003-2788-0303</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865650/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865650/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35130274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Waespy, Mario</creatorcontrib><creatorcontrib>Gbem, Thaddeus Termulun</creatorcontrib><creatorcontrib>Dinesh Kumar, Nilima</creatorcontrib><creatorcontrib>Solaiyappan Mani, Shanmugam</creatorcontrib><creatorcontrib>Rosenau, Jana</creatorcontrib><creatorcontrib>Dietz, Frank</creatorcontrib><creatorcontrib>Kelm, Sørge</creatorcontrib><title>Cooperativity of catalytic and lectin-like domain of Trypanosoma congolense trans-sialidase modulates its catalytic activity</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Trans-sialidases (TS) represent a multi-gene family of unusual enzymes, which catalyse the transfer of terminal sialic acids (Sia) from sialoglycoconjugates to terminal galactose or N-acetylgalactosamine residues of oligosaccharides without the requirement of CMP-Neu5Ac, the activated Sia used by typical sialyltransferases. Enzymes comprise a N-terminal catalytic domain (CD) followed by a lectin-like domain (LD). Most work on trypanosomal TS has been done on enzymatic activities focusing on the CD of TS from Trypanosoma cruzi (causing Chagas disease in Latin America), subspecies of Trypanosoma brucei, (causing human sleeping sickness in Africa) and Trypanosoma congolense (causing African Animal Trypanosomosis in livestock). Previously, we demonstrated that T. congolense TS (TconTS)-LD binds to several carbohydrates, such as 1,4-β-mannotriose. In this study we investigated the influence of TconTS3-LD on Sia transfer efficiency of TconTS1a-CD by swapping domains. in silico analysis on structure models of TconTS enzymes revealed the potential of domain swaps between TconTS1a and TconTS3 without structural disruptions of the enzymes overall topologies. Recombinant domain swapped TconTS1a/TS3 showed clear Sia transfer activity, when using fetuin and lactose as Sia donor and acceptor substrates, respectively. While Sia transfer activity remained unchanged from the level of TconTS1a, hydrolytic release of free Neu5Ac as a side product was suppressed resulting in increased transfer efficiency. Presence of 1,4-β-mannotriose during TS reactions modulates enzyme activities enhancing transfer efficiency possibly due to occupation of the binding site in TconTS1a-LD. Interestingly this effect was in the same range as that observed when swapping TconTS1a-CD and TconTS3-LD. In summary, this study demonstrate the proof-of-principle for swapping CDs and LDs of TconTS and that TconTS3-LD influences enzymatic activity of TconTS1a-CD providing evidence that LDs play pivotal roles in modulating activities and biological functions of TconTS and possibly other TS.</description><subject>Acetylgalactosamine - metabolism</subject><subject>African trypanosomiasis</subject><subject>Amino acids</subject><subject>Binding Sites</subject><subject>Biology and Life Sciences</subject><subject>Carbohydrates</subject><subject>Catalysis</subject><subject>Catalytic activity</subject><subject>Chagas disease</subject><subject>Chemical properties</subject><subject>Domains</subject><subject>Efficiency</subject><subject>Enzymatic activity</subject><subject>Enzymatic analysis</subject><subject>Enzyme activity</subject><subject>Enzymes</subject><subject>Galactose</subject><subject>Galactose - metabolism</subject><subject>Glycoproteins</subject><subject>Glycoproteins - chemistry</subject><subject>Glycoproteins - genetics</subject><subject>Glycoproteins - metabolism</subject><subject>Lactose</subject><subject>Ligands</subject><subject>Livestock</subject><subject>Methods</subject><subject>N-Acetylgalactosamine</subject><subject>Neuraminidase - chemistry</subject><subject>Neuraminidase - genetics</subject><subject>Neuraminidase - metabolism</subject><subject>Oligosaccharides</subject><subject>Oligosaccharides - metabolism</subject><subject>Parasites</subject><subject>Physical Sciences</subject><subject>Proteins</subject><subject>Protozoan Proteins - chemistry</subject><subject>Protozoan Proteins - genetics</subject><subject>Protozoan Proteins - metabolism</subject><subject>Recombinants</subject><subject>Research and Analysis Methods</subject><subject>Sialic acids</subject><subject>Sialic Acids - metabolism</subject><subject>Substrates</subject><subject>Topology</subject><subject>trans-Sialidase</subject><subject>Tropical diseases</subject><subject>Trypanosoma</subject><subject>Trypanosoma congolense</subject><subject>Trypanosoma congolense - 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chemistry</topic><topic>Protozoan Proteins - genetics</topic><topic>Protozoan Proteins - metabolism</topic><topic>Recombinants</topic><topic>Research and Analysis Methods</topic><topic>Sialic acids</topic><topic>Sialic Acids - metabolism</topic><topic>Substrates</topic><topic>Topology</topic><topic>trans-Sialidase</topic><topic>Tropical diseases</topic><topic>Trypanosoma</topic><topic>Trypanosoma congolense</topic><topic>Trypanosoma congolense - chemistry</topic><topic>Trypanosoma congolense - enzymology</topic><topic>Trypanosoma congolense - genetics</topic><topic>Varieties</topic><topic>Vector-borne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Waespy, Mario</creatorcontrib><creatorcontrib>Gbem, Thaddeus Termulun</creatorcontrib><creatorcontrib>Dinesh Kumar, Nilima</creatorcontrib><creatorcontrib>Solaiyappan Mani, Shanmugam</creatorcontrib><creatorcontrib>Rosenau, Jana</creatorcontrib><creatorcontrib>Dietz, Frank</creatorcontrib><creatorcontrib>Kelm, Sørge</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Waespy, Mario</au><au>Gbem, Thaddeus Termulun</au><au>Dinesh Kumar, Nilima</au><au>Solaiyappan Mani, Shanmugam</au><au>Rosenau, Jana</au><au>Dietz, Frank</au><au>Kelm, Sørge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cooperativity of catalytic and lectin-like domain of Trypanosoma congolense trans-sialidase modulates its catalytic activity</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>16</volume><issue>2</issue><spage>e0009585</spage><pages>e0009585-</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Trans-sialidases (TS) represent a multi-gene family of unusual enzymes, which catalyse the transfer of terminal sialic acids (Sia) from sialoglycoconjugates to terminal galactose or N-acetylgalactosamine residues of oligosaccharides without the requirement of CMP-Neu5Ac, the activated Sia used by typical sialyltransferases. Enzymes comprise a N-terminal catalytic domain (CD) followed by a lectin-like domain (LD). Most work on trypanosomal TS has been done on enzymatic activities focusing on the CD of TS from Trypanosoma cruzi (causing Chagas disease in Latin America), subspecies of Trypanosoma brucei, (causing human sleeping sickness in Africa) and Trypanosoma congolense (causing African Animal Trypanosomosis in livestock). Previously, we demonstrated that T. congolense TS (TconTS)-LD binds to several carbohydrates, such as 1,4-β-mannotriose. In this study we investigated the influence of TconTS3-LD on Sia transfer efficiency of TconTS1a-CD by swapping domains. in silico analysis on structure models of TconTS enzymes revealed the potential of domain swaps between TconTS1a and TconTS3 without structural disruptions of the enzymes overall topologies. Recombinant domain swapped TconTS1a/TS3 showed clear Sia transfer activity, when using fetuin and lactose as Sia donor and acceptor substrates, respectively. While Sia transfer activity remained unchanged from the level of TconTS1a, hydrolytic release of free Neu5Ac as a side product was suppressed resulting in increased transfer efficiency. Presence of 1,4-β-mannotriose during TS reactions modulates enzyme activities enhancing transfer efficiency possibly due to occupation of the binding site in TconTS1a-LD. Interestingly this effect was in the same range as that observed when swapping TconTS1a-CD and TconTS3-LD. In summary, this study demonstrate the proof-of-principle for swapping CDs and LDs of TconTS and that TconTS3-LD influences enzymatic activity of TconTS1a-CD providing evidence that LDs play pivotal roles in modulating activities and biological functions of TconTS and possibly other TS.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35130274</pmid><doi>10.1371/journal.pntd.0009585</doi><orcidid>https://orcid.org/0000-0003-2757-0786</orcidid><orcidid>https://orcid.org/0000-0003-0039-5770</orcidid><orcidid>https://orcid.org/0000-0002-9341-8187</orcidid><orcidid>https://orcid.org/0000-0001-5277-9421</orcidid><orcidid>https://orcid.org/0000-0002-2366-0082</orcidid><orcidid>https://orcid.org/0000-0003-2788-0303</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2022-02, Vol.16 (2), p.e0009585 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_2640118542 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Acetylgalactosamine - metabolism African trypanosomiasis Amino acids Binding Sites Biology and Life Sciences Carbohydrates Catalysis Catalytic activity Chagas disease Chemical properties Domains Efficiency Enzymatic activity Enzymatic analysis Enzyme activity Enzymes Galactose Galactose - metabolism Glycoproteins Glycoproteins - chemistry Glycoproteins - genetics Glycoproteins - metabolism Lactose Ligands Livestock Methods N-Acetylgalactosamine Neuraminidase - chemistry Neuraminidase - genetics Neuraminidase - metabolism Oligosaccharides Oligosaccharides - metabolism Parasites Physical Sciences Proteins Protozoan Proteins - chemistry Protozoan Proteins - genetics Protozoan Proteins - metabolism Recombinants Research and Analysis Methods Sialic acids Sialic Acids - metabolism Substrates Topology trans-Sialidase Tropical diseases Trypanosoma Trypanosoma congolense Trypanosoma congolense - chemistry Trypanosoma congolense - enzymology Trypanosoma congolense - genetics Varieties Vector-borne diseases |
| title | Cooperativity of catalytic and lectin-like domain of Trypanosoma congolense trans-sialidase modulates its catalytic activity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T23%3A16%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cooperativity%20of%20catalytic%20and%20lectin-like%20domain%20of%20Trypanosoma%20congolense%20trans-sialidase%20modulates%20its%20catalytic%20activity&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Waespy,%20Mario&rft.date=2022-02-01&rft.volume=16&rft.issue=2&rft.spage=e0009585&rft.pages=e0009585-&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0009585&rft_dat=%3Cgale_plos_%3EA696086026%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2640118542&rft_id=info:pmid/35130274&rft_galeid=A696086026&rft_doaj_id=oai_doaj_org_article_92619b44b35843adb936cd8eb72626d8&rfr_iscdi=true |