3,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5’-phosphate for cuticle assembly in the mosquito Aedes aegypti
Abstract 3,4-Dihydroxyphenylacetaldehyde synthase (DHPAAS) catalyzes oxygen-dependent conversion of 3,4-dihydroxyphenylalanine (dopa) to 3,4-dihydroxyphenylacetaldehyde (DHPAA), a likely cross-linking agent precursor of the insect cuticle. In the current study, extensive in vivo experiments in Aedes...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59723-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849326837018132480 |
|---|---|
| author | Jing Chen Christopher J. Vavricka Shuangshuang Wei Yasumoto Nakazawa Yuri Matsumoto Huaqing Chen Yu Tang Jing Liang Jiukai Chen Yaneng Huang Keiichi Noguchi Tomohisa Hasunuma Huai Guan Jianyong Li Chenghong Liao Qian Han |
| author_facet | Jing Chen Christopher J. Vavricka Shuangshuang Wei Yasumoto Nakazawa Yuri Matsumoto Huaqing Chen Yu Tang Jing Liang Jiukai Chen Yaneng Huang Keiichi Noguchi Tomohisa Hasunuma Huai Guan Jianyong Li Chenghong Liao Qian Han |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | Abstract 3,4-Dihydroxyphenylacetaldehyde synthase (DHPAAS) catalyzes oxygen-dependent conversion of 3,4-dihydroxyphenylalanine (dopa) to 3,4-dihydroxyphenylacetaldehyde (DHPAA), a likely cross-linking agent precursor of the insect cuticle. In the current study, extensive in vivo experiments in Aedes aegypti show that DHPAAS is essential for abdominal integrity, egg development and cuticle structure formation. Solid-state 13C nuclear magnetic resonance analysis of the Ae. aegypti cuticle molecular structure shows chemical shifts of 115 to 145 ppm, suggesting the presence of catechols derived from DHPAA. The crystal structure of insect DHPAAS was then solved, revealing an active site that is divergent from that of the homologous enzyme dopa decarboxylase. In the DHPAAS crystal structure, stabilization of the flexible 320–350 region accompanies the positioning of the 350–360 loop relatively close to the catalytic Asn192 residue while the conserved active site residue Phe103 adopts an open conformation away from the active center; these distinct features participate in the formation of a specific hydrophobic tunnel which potentially facilitates delivery of oxygen to pyridoxal 5’-phosphate in the conversion of dopa to DHPAA. |
| format | Article |
| id | doaj-art-7a78d1ae68f2433daece2cbf712e8551 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7a78d1ae68f2433daece2cbf712e85512025-08-20T03:48:02ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-59723-03,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5’-phosphate for cuticle assembly in the mosquito Aedes aegyptiJing Chen0Christopher J. Vavricka1Shuangshuang Wei2Yasumoto Nakazawa3Yuri Matsumoto4Huaqing Chen5Yu Tang6Jing Liang7Jiukai Chen8Yaneng Huang9Keiichi Noguchi10Tomohisa Hasunuma11Huai Guan12Jianyong Li13Chenghong Liao14Qian Han15Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityDepartment of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, KoganeiLaboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityDepartment of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, KoganeiDepartment of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, KoganeiLaboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityLaboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityDepartment of Biochemistry, Virginia Polytechnic Institute and State UniversityLaboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityLaboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityDepartment of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, KoganeiEngineering Biology Research Center, Kobe UniversityLaboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityDepartment of Biochemistry, Virginia Polytechnic Institute and State UniversityLaboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityLaboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan UniversityAbstract 3,4-Dihydroxyphenylacetaldehyde synthase (DHPAAS) catalyzes oxygen-dependent conversion of 3,4-dihydroxyphenylalanine (dopa) to 3,4-dihydroxyphenylacetaldehyde (DHPAA), a likely cross-linking agent precursor of the insect cuticle. In the current study, extensive in vivo experiments in Aedes aegypti show that DHPAAS is essential for abdominal integrity, egg development and cuticle structure formation. Solid-state 13C nuclear magnetic resonance analysis of the Ae. aegypti cuticle molecular structure shows chemical shifts of 115 to 145 ppm, suggesting the presence of catechols derived from DHPAA. The crystal structure of insect DHPAAS was then solved, revealing an active site that is divergent from that of the homologous enzyme dopa decarboxylase. In the DHPAAS crystal structure, stabilization of the flexible 320–350 region accompanies the positioning of the 350–360 loop relatively close to the catalytic Asn192 residue while the conserved active site residue Phe103 adopts an open conformation away from the active center; these distinct features participate in the formation of a specific hydrophobic tunnel which potentially facilitates delivery of oxygen to pyridoxal 5’-phosphate in the conversion of dopa to DHPAA.https://doi.org/10.1038/s41467-025-59723-0 |
| spellingShingle | Jing Chen Christopher J. Vavricka Shuangshuang Wei Yasumoto Nakazawa Yuri Matsumoto Huaqing Chen Yu Tang Jing Liang Jiukai Chen Yaneng Huang Keiichi Noguchi Tomohisa Hasunuma Huai Guan Jianyong Li Chenghong Liao Qian Han 3,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5’-phosphate for cuticle assembly in the mosquito Aedes aegypti Nature Communications |
| title | 3,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5’-phosphate for cuticle assembly in the mosquito Aedes aegypti |
| title_full | 3,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5’-phosphate for cuticle assembly in the mosquito Aedes aegypti |
| title_fullStr | 3,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5’-phosphate for cuticle assembly in the mosquito Aedes aegypti |
| title_full_unstemmed | 3,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5’-phosphate for cuticle assembly in the mosquito Aedes aegypti |
| title_short | 3,4-Dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5’-phosphate for cuticle assembly in the mosquito Aedes aegypti |
| title_sort | 3 4 dihydroxyphenylacetaldehyde synthase evolved an ordered structure to deliver oxygen to pyridoxal 5 phosphate for cuticle assembly in the mosquito aedes aegypti |
| url | https://doi.org/10.1038/s41467-025-59723-0 |
| work_keys_str_mv | AT jingchen 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT christopherjvavricka 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT shuangshuangwei 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT yasumotonakazawa 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT yurimatsumoto 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT huaqingchen 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT yutang 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT jingliang 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT jiukaichen 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT yanenghuang 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT keiichinoguchi 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT tomohisahasunuma 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT huaiguan 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT jianyongli 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT chenghongliao 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti AT qianhan 34dihydroxyphenylacetaldehydesynthaseevolvedanorderedstructuretodeliveroxygentopyridoxal5phosphateforcuticleassemblyinthemosquitoaedesaegypti |