Conformational Changes in a Macrolide Antibiotic Binding Protein From Mycobacterium smegmatis Upon ADP Binding
Rv3197 (MABP-1), a non-canonical ABC protein in Mycobacterium tuberculosis, has ATPase activity and confers inducible resistance to the macrolide family of antibiotics. Here we have shown that MSMEG_1954, the homolog of Rv3197 in M. smegmatis, has a similar function of conferring macrolide resistanc...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.780954/full |
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| author | Qingqing Zhang Qingqing Zhang Xiang Liu Huijuan Liu Bingjie Zhang Haitao Yang Kaixia Mi Luke W. Guddat Zihe Rao Zihe Rao Zihe Rao |
| author_facet | Qingqing Zhang Qingqing Zhang Xiang Liu Huijuan Liu Bingjie Zhang Haitao Yang Kaixia Mi Luke W. Guddat Zihe Rao Zihe Rao Zihe Rao |
| author_sort | Qingqing Zhang |
| collection | DOAJ |
| description | Rv3197 (MABP-1), a non-canonical ABC protein in Mycobacterium tuberculosis, has ATPase activity and confers inducible resistance to the macrolide family of antibiotics. Here we have shown that MSMEG_1954, the homolog of Rv3197 in M. smegmatis, has a similar function of conferring macrolide resistance. Crystal structures of apo-MSMEG_1954 (form1 and form 2) and MSMEG_1954 in complex with ADP have been determined. These three structures show that MSMEG_1954 has at least two different conformations we identify as closed state (MSMEG_1954-form 1) and open state (MSMEG_1954-form 2 and MSMEG_1954-ADP). Structural superimposition shows that the MSMEG_1954-form 2 and MSMEG_1954-ADP complex have similar conformation to that observed for MABP-1 and MABP-1-erythromicin complex structure. However, the antibiotic binding pocket in MSMEG_1954-form 1 is completely blocked by the N-terminal accessory domain. When bound by ADP, the N-terminal accessory domain undergoes conformational change, which results in the open of the antibiotic binding pocket. Because of the degradation of N terminal accessory domain in MSMSG_1954-form 2, it is likely to represent a transitional state between MSMEG_1954-form 1 and MSMEG_1954-ADP complex structure. |
| first_indexed | 2024-12-14T08:38:38Z |
| format | Article |
| id | doaj.art-2250ac4a60b543128b47ac2be421ee73 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-14T08:38:38Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-2250ac4a60b543128b47ac2be421ee732022-12-21T23:09:21ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-12-011210.3389/fmicb.2021.780954780954Conformational Changes in a Macrolide Antibiotic Binding Protein From Mycobacterium smegmatis Upon ADP BindingQingqing Zhang0Qingqing Zhang1Xiang Liu2Huijuan Liu3Bingjie Zhang4Haitao Yang5Kaixia Mi6Luke W. Guddat7Zihe Rao8Zihe Rao9Zihe Rao10State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, ChinaInnovative Center for Pathogen Research, Guangzhou Laboratory, Guangzhou, ChinaState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, ChinaState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaShanghai Institute for Advanced Immunochemical Studies and School of Life Sciences and Technology, ShanghaiTech University, Shanghai, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, AustraliaState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, ChinaShanghai Institute for Advanced Immunochemical Studies and School of Life Sciences and Technology, ShanghaiTech University, Shanghai, ChinaLaboratory of Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, ChinaRv3197 (MABP-1), a non-canonical ABC protein in Mycobacterium tuberculosis, has ATPase activity and confers inducible resistance to the macrolide family of antibiotics. Here we have shown that MSMEG_1954, the homolog of Rv3197 in M. smegmatis, has a similar function of conferring macrolide resistance. Crystal structures of apo-MSMEG_1954 (form1 and form 2) and MSMEG_1954 in complex with ADP have been determined. These three structures show that MSMEG_1954 has at least two different conformations we identify as closed state (MSMEG_1954-form 1) and open state (MSMEG_1954-form 2 and MSMEG_1954-ADP). Structural superimposition shows that the MSMEG_1954-form 2 and MSMEG_1954-ADP complex have similar conformation to that observed for MABP-1 and MABP-1-erythromicin complex structure. However, the antibiotic binding pocket in MSMEG_1954-form 1 is completely blocked by the N-terminal accessory domain. When bound by ADP, the N-terminal accessory domain undergoes conformational change, which results in the open of the antibiotic binding pocket. Because of the degradation of N terminal accessory domain in MSMSG_1954-form 2, it is likely to represent a transitional state between MSMEG_1954-form 1 and MSMEG_1954-ADP complex structure.https://www.frontiersin.org/articles/10.3389/fmicb.2021.780954/fullcrystal structureconformational changemacrolide antibiotic binding protein (MABP)non-canonical ABC transportermacrolide antibioticerythromycin |
| spellingShingle | Qingqing Zhang Qingqing Zhang Xiang Liu Huijuan Liu Bingjie Zhang Haitao Yang Kaixia Mi Luke W. Guddat Zihe Rao Zihe Rao Zihe Rao Conformational Changes in a Macrolide Antibiotic Binding Protein From Mycobacterium smegmatis Upon ADP Binding Frontiers in Microbiology crystal structure conformational change macrolide antibiotic binding protein (MABP) non-canonical ABC transporter macrolide antibiotic erythromycin |
| title | Conformational Changes in a Macrolide Antibiotic Binding Protein From Mycobacterium smegmatis Upon ADP Binding |
| title_full | Conformational Changes in a Macrolide Antibiotic Binding Protein From Mycobacterium smegmatis Upon ADP Binding |
| title_fullStr | Conformational Changes in a Macrolide Antibiotic Binding Protein From Mycobacterium smegmatis Upon ADP Binding |
| title_full_unstemmed | Conformational Changes in a Macrolide Antibiotic Binding Protein From Mycobacterium smegmatis Upon ADP Binding |
| title_short | Conformational Changes in a Macrolide Antibiotic Binding Protein From Mycobacterium smegmatis Upon ADP Binding |
| title_sort | conformational changes in a macrolide antibiotic binding protein from mycobacterium smegmatis upon adp binding |
| topic | crystal structure conformational change macrolide antibiotic binding protein (MABP) non-canonical ABC transporter macrolide antibiotic erythromycin |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.780954/full |
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