Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3
MICAL is an oxidoreductase that participates in cytoskeleton reorganization via actin disassembly in the presence of NADPH. Although three MICALs (MICAL1, MICAL2 and MICAL3) have been identified in mammals, only the structure of mouse MICAL1 has been reported. Here, the first crystal structure of hu...
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| Format: | Article |
| Language: | English |
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International Union of Crystallography
2020-01-01
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| Series: | IUCrJ |
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| Online Access: | http://scripts.iucr.org/cgi-bin/paper?S2052252519015409 |
| _version_ | 1818321889496399872 |
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| author | Junsoo Kim Haemin Lee Yeon Jin Roh Han-ul Kim Donghyuk Shin Sorah Kim Jonghyeon Son Aro Lee Minseo Kim Junga Park Seong Yun Hwang Kyunghwan Kim Yong Kwon Lee Hyun Suk Jung Kwang Yeon Hwang Byung Cheon Lee |
| author_facet | Junsoo Kim Haemin Lee Yeon Jin Roh Han-ul Kim Donghyuk Shin Sorah Kim Jonghyeon Son Aro Lee Minseo Kim Junga Park Seong Yun Hwang Kyunghwan Kim Yong Kwon Lee Hyun Suk Jung Kwang Yeon Hwang Byung Cheon Lee |
| author_sort | Junsoo Kim |
| collection | DOAJ |
| description | MICAL is an oxidoreductase that participates in cytoskeleton reorganization via actin disassembly in the presence of NADPH. Although three MICALs (MICAL1, MICAL2 and MICAL3) have been identified in mammals, only the structure of mouse MICAL1 has been reported. Here, the first crystal structure of human MICAL3, which contains the flavin-containing monooxygenase (FMO) and calponin-homology (CH) domains, is reported. MICAL3 has an FAD/NADP-binding Rossmann-fold domain for monooxygenase activity like MICAL1. The FMO and CH domains of both MICAL3 and MICAL1 are highly similar in structure, but superimposition of the two structures shows a different relative position of the CH domain in the asymmetric unit. Based on kinetic analyses, the catalytic efficiency of MICAL3 dramatically increased on adding F-actin only when the CH domain was available. However, this did not occur when two residues, Glu213 and Arg530, were mutated in the FMO and CH domains, respectively. Overall, MICAL3 is structurally highly similar to MICAL1, which suggests that they may adopt the same catalytic mechanism, but the difference in the relative position of the CH domain produces a difference in F-actin substrate specificity. |
| first_indexed | 2024-12-13T10:48:04Z |
| format | Article |
| id | doaj.art-87547a1bbd2b4708aa070890f7af20ec |
| institution | Directory Open Access Journal |
| issn | 2052-2525 |
| language | English |
| last_indexed | 2024-12-13T10:48:04Z |
| publishDate | 2020-01-01 |
| publisher | International Union of Crystallography |
| record_format | Article |
| series | IUCrJ |
| spelling | doaj.art-87547a1bbd2b4708aa070890f7af20ec2022-12-21T23:50:03ZengInternational Union of CrystallographyIUCrJ2052-25252020-01-0171909910.1107/S2052252519015409lz5030Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3Junsoo Kim0Haemin Lee1Yeon Jin Roh2Han-ul Kim3Donghyuk Shin4Sorah Kim5Jonghyeon Son6Aro Lee7Minseo Kim8Junga Park9Seong Yun Hwang10Kyunghwan Kim11Yong Kwon Lee12Hyun Suk Jung13Kwang Yeon Hwang14Byung Cheon Lee15College of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaBiochemistry Laboratory, Department of Biosystems and Biotechnology, Kangwon National University, 1 Kangwondaekak-gil, Chuncheon-si, Gangwon-do 24341, Republic of KoreaBuchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main, GermanyCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaDepartment of Biology, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of KoreaDepartment of Biology, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of KoreaDepartment of Culinary Art and Food Service Management, Yuhan University, 590 Gyeongin-ro, Bucheon-si, Gyeonggi-do 14780, Republic of KoreaBiochemistry Laboratory, Department of Biosystems and Biotechnology, Kangwon National University, 1 Kangwondaekak-gil, Chuncheon-si, Gangwon-do 24341, Republic of KoreaCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaCollege of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of KoreaMICAL is an oxidoreductase that participates in cytoskeleton reorganization via actin disassembly in the presence of NADPH. Although three MICALs (MICAL1, MICAL2 and MICAL3) have been identified in mammals, only the structure of mouse MICAL1 has been reported. Here, the first crystal structure of human MICAL3, which contains the flavin-containing monooxygenase (FMO) and calponin-homology (CH) domains, is reported. MICAL3 has an FAD/NADP-binding Rossmann-fold domain for monooxygenase activity like MICAL1. The FMO and CH domains of both MICAL3 and MICAL1 are highly similar in structure, but superimposition of the two structures shows a different relative position of the CH domain in the asymmetric unit. Based on kinetic analyses, the catalytic efficiency of MICAL3 dramatically increased on adding F-actin only when the CH domain was available. However, this did not occur when two residues, Glu213 and Arg530, were mutated in the FMO and CH domains, respectively. Overall, MICAL3 is structurally highly similar to MICAL1, which suggests that they may adopt the same catalytic mechanism, but the difference in the relative position of the CH domain produces a difference in F-actin substrate specificity.http://scripts.iucr.org/cgi-bin/paper?S2052252519015409micalactin depolymerizationcalponin-homology domainf-actinmonooxygenasesstructure determinationprotein structurerefinementx-ray crystallographyenzyme mechanisms |
| spellingShingle | Junsoo Kim Haemin Lee Yeon Jin Roh Han-ul Kim Donghyuk Shin Sorah Kim Jonghyeon Son Aro Lee Minseo Kim Junga Park Seong Yun Hwang Kyunghwan Kim Yong Kwon Lee Hyun Suk Jung Kwang Yeon Hwang Byung Cheon Lee Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3 IUCrJ mical actin depolymerization calponin-homology domain f-actin monooxygenases structure determination protein structure refinement x-ray crystallography enzyme mechanisms |
| title | Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3 |
| title_full | Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3 |
| title_fullStr | Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3 |
| title_full_unstemmed | Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3 |
| title_short | Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3 |
| title_sort | structural and kinetic insights into flavin containing monooxygenase and calponin homology domains in human mical3 |
| topic | mical actin depolymerization calponin-homology domain f-actin monooxygenases structure determination protein structure refinement x-ray crystallography enzyme mechanisms |
| url | http://scripts.iucr.org/cgi-bin/paper?S2052252519015409 |
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