| Autor: |
James L. Hougland, Michelle A. Sieburg, Kayleigh R. McGovern-Gooch, Tasha R. Davis, Maria B. Campaña, Mohammad Ashkar, Rosemary Loftus, Najae Escoffery, Flaviyan Jerome Irudayanathan, Melissa Navarro, Shikha Nangia |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| DOI: |
10.1101/556233 |
| Popis: |
Integral membrane proteins represent a large and essential portion of the proteome that often prove challenging for structural studies. We demonstrate a synergistic approach to structurally model topologically complex integral membrane proteins by combining co-evolutionary constraints and computational modeling with biochemical validation. We report the first structural model of a eukaryotic membrane-bound O-acyltransferase (MBOAT), ghrelin O-acyltransferase (GOAT), which modifies the metabolism-regulating hormone ghrelin. Our structure suggests an unanticipated strategy for trans-membrane protein acylation, with catalysis occurring in an internal channel as GOAT acts as an “enzyme inside a pore”. Our structure opens the door to structure-guided inhibitor design targeting GOAT and other MBOAT family members while validating the power of our approach to generate predictive structural models for other experimentally challenging integral membrane proteins. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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