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Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria
Some bacterial type II fatty-acid synthesis (FAS II) enzymes have been shown to be important candidates for drug discovery. The scientific and medical quest for new FAS II protein targets continues to stimulate research in this field. One of the possible additional candidates is the acyl-carrier-pro...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447402/ https://www.ncbi.nlm.nih.gov/pubmed/22993090 http://dx.doi.org/10.1107/S0907444912029101 |
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author | Halavaty, Andrei S. Kim, Youngchang Minasov, George Shuvalova, Ludmilla Dubrovska, Ievgeniia Winsor, James Zhou, Min Onopriyenko, Olena Skarina, Tatiana Papazisi, Leka Kwon, Keehwan Peterson, Scott N. Joachimiak, Andrzej Savchenko, Alexei Anderson, Wayne F. |
author_facet | Halavaty, Andrei S. Kim, Youngchang Minasov, George Shuvalova, Ludmilla Dubrovska, Ievgeniia Winsor, James Zhou, Min Onopriyenko, Olena Skarina, Tatiana Papazisi, Leka Kwon, Keehwan Peterson, Scott N. Joachimiak, Andrzej Savchenko, Alexei Anderson, Wayne F. |
author_sort | Halavaty, Andrei S. |
collection | PubMed |
description | Some bacterial type II fatty-acid synthesis (FAS II) enzymes have been shown to be important candidates for drug discovery. The scientific and medical quest for new FAS II protein targets continues to stimulate research in this field. One of the possible additional candidates is the acyl-carrier-protein synthase (AcpS) enzyme. Its holo form post-translationally modifies the apo form of an acyl carrier protein (ACP), which assures the constant delivery of thioester intermediates to the discrete enzymes of FAS II. At the Center for Structural Genomics of Infectious Diseases (CSGID), AcpSs from Staphylococcus aureus (AcpS(SA)), Vibrio cholerae (AcpS(VC)) and Bacillus anthracis (AcpS(BA)) have been structurally characterized in their apo, holo and product-bound forms, respectively. The structure of AcpS(BA) is emphasized because of the two 3′,5′-adenosine diphosphate (3′,5′-ADP) product molecules that are found in each of the three coenzyme A (CoA) binding sites of the trimeric protein. One 3′,5′-ADP is bound as the 3′,5′-ADP part of CoA in the known structures of the CoA–AcpS and 3′,5′-ADP–AcpS binary complexes. The position of the second 3′,5′-ADP has never been described before. It is in close proximity to the first 3′,5′-ADP and the ACP-binding site. The coordination of two ADPs in AcpS(BA) may possibly be exploited for the design of AcpS inhibitors that can block binding of both CoA and ACP. |
format | Online Article Text |
id | pubmed-3447402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-34474022012-09-20 Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria Halavaty, Andrei S. Kim, Youngchang Minasov, George Shuvalova, Ludmilla Dubrovska, Ievgeniia Winsor, James Zhou, Min Onopriyenko, Olena Skarina, Tatiana Papazisi, Leka Kwon, Keehwan Peterson, Scott N. Joachimiak, Andrzej Savchenko, Alexei Anderson, Wayne F. Acta Crystallogr D Biol Crystallogr Research Papers Some bacterial type II fatty-acid synthesis (FAS II) enzymes have been shown to be important candidates for drug discovery. The scientific and medical quest for new FAS II protein targets continues to stimulate research in this field. One of the possible additional candidates is the acyl-carrier-protein synthase (AcpS) enzyme. Its holo form post-translationally modifies the apo form of an acyl carrier protein (ACP), which assures the constant delivery of thioester intermediates to the discrete enzymes of FAS II. At the Center for Structural Genomics of Infectious Diseases (CSGID), AcpSs from Staphylococcus aureus (AcpS(SA)), Vibrio cholerae (AcpS(VC)) and Bacillus anthracis (AcpS(BA)) have been structurally characterized in their apo, holo and product-bound forms, respectively. The structure of AcpS(BA) is emphasized because of the two 3′,5′-adenosine diphosphate (3′,5′-ADP) product molecules that are found in each of the three coenzyme A (CoA) binding sites of the trimeric protein. One 3′,5′-ADP is bound as the 3′,5′-ADP part of CoA in the known structures of the CoA–AcpS and 3′,5′-ADP–AcpS binary complexes. The position of the second 3′,5′-ADP has never been described before. It is in close proximity to the first 3′,5′-ADP and the ACP-binding site. The coordination of two ADPs in AcpS(BA) may possibly be exploited for the design of AcpS inhibitors that can block binding of both CoA and ACP. International Union of Crystallography 2012-10-01 2012-09-13 /pmc/articles/PMC3447402/ /pubmed/22993090 http://dx.doi.org/10.1107/S0907444912029101 Text en © Halavaty et al. 2012 http://creativecommons.org/licenses/by/2.0/uk/ This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. |
spellingShingle | Research Papers Halavaty, Andrei S. Kim, Youngchang Minasov, George Shuvalova, Ludmilla Dubrovska, Ievgeniia Winsor, James Zhou, Min Onopriyenko, Olena Skarina, Tatiana Papazisi, Leka Kwon, Keehwan Peterson, Scott N. Joachimiak, Andrzej Savchenko, Alexei Anderson, Wayne F. Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria |
title | Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria |
title_full | Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria |
title_fullStr | Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria |
title_full_unstemmed | Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria |
title_short | Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria |
title_sort | structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447402/ https://www.ncbi.nlm.nih.gov/pubmed/22993090 http://dx.doi.org/10.1107/S0907444912029101 |
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