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Crystal structure of human trans-3-Hydroxy-L-proline dehydratase
Structural highlights
FunctionT3HPD_HUMAN Catalyzes the dehydration of trans-3-hydroxy-L-proline to Delta(1)-pyrroline-2-carboxylate (Pyr2C). May be required to degrade trans-3-hydroxy-L-proline from the diet and originating from the degradation of proteins such as collagen-IV that contain it.[1] Publication Abstract from PubMedComputational methods for protein structure prediction have made significant strides forward, as evidenced by the last development of the neural network AlphaFold, which outperformed the CASP14 competitors by consistently predicting the structure of target proteins. Here we show an integrated structural investigation that combines the AlphaFold and crystal structures of human trans-3-Hydroxy-l-proline dehydratase, an enzyme involved in hydroxyproline catabolism and whose structure had never been reported before, identifying a structural element, absent in the AlphaFold model but present in the crystal structure, that was subsequently proved to be functionally relevant. Although the AlphaFold model lacked information on protein oligomerization, the native dimer was reconstructed using template-based and ab initio computational approaches. Moreover, molecular phasing of the diffraction data using the AlphaFold model resulted in dimer reconstruction and straightforward structure solution. Our work adds to the integration of AlphaFold with experimental structural and functional data for protein analysis, crystallographic phasing and structure solution. The integration of AlphaFold-predicted and crystal structures of human trans-3-hydroxy-l-proline dehydratase reveals a regulatory catalytic mechanism.,Ferrario E, Miggiano R, Rizzi M, Ferraris DM Comput Struct Biotechnol J. 2022 Jul 18;20:3874-3883. doi: , 10.1016/j.csbj.2022.07.027. eCollection 2022. PMID:35891782[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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