FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3067746620> ?p ?o ?g. }

• W3067746620 endingPage "190" @default.
• W3067746620 startingPage "180" @default.
• W3067746620 abstract "Two mechanisms, induced fit (IF) and conformational selection (CS), have been proposed to explain ligand recognition coupled conformational changes. The histidine binding protein (HisJ) adopts the CS mechanism, in which a pre-equilibrium is established between the open and the closed states with the ligand binding to the closed state. Despite being structurally similar to HisJ, the maltose binding protein (MBP) adopts the IF mechanism, in which the ligand binds the open state and induces a transition to the closed state. To understand the molecular determinants of this difference, we performed molecular dynamics (MD) simulations of coarse-grained dual structure based models. We find that intra-protein contacts unique to the closed state are sufficient to promote the conformational transition in HisJ, indicating a CS-like mechanism. In contrast, additional ligand-mimicking contacts are required to “induce” the conformational transition in MBP suggesting an IF-like mechanism. In agreement with experiments, destabilizing modifications to two structural features, the spine helix (SH) and the balancing interface (BI), present in MBP but absent in HisJ, reduce the need for ligand-mimicking contacts indicating that SH and BI act as structural restraints that keep MBP in the open state. We introduce an SH like element into HisJ and observe that this can impede the conformational transition increasing the importance of ligand-mimicking contacts. Similarly, simultaneous mutations to BI and SH in MBP reduce the barrier to conformational transitions significantly and promote a CS-like mechanism. Together, our results show that structural restraints present in the protein structure can determine the mechanism of conformational transitions and even simple models that correctly capture such structural features can predict their positions. MD simulations of such models can thus be used, in conjunction with mutational experiments, to regulate protein ligand interactions, and modulate ligand binding affinities." @default.
• W3067746620 created "2020-08-24" @default.
• W3067746620 creator A5015471381 @default.
• W3067746620 creator A5034743915 @default.
• W3067746620 creator A5056115805 @default.
• W3067746620 date "2020-01-01" @default.
• W3067746620 modified "2023-09-26" @default.
• W3067746620 title "Structure dictates the mechanism of ligand recognition in the histidine and maltose binding proteins" @default.
• W3067746620 cites W1492554871 @default.
• W3067746620 cites W1517660339 @default.
• W3067746620 cites W1593975599 @default.
• W3067746620 cites W1594136944 @default.
• W3067746620 cites W1964604281 @default.
• W3067746620 cites W1975818112 @default.
• W3067746620 cites W1981101212 @default.
• W3067746620 cites W1981369098 @default.
• W3067746620 cites W1987679703 @default.
• W3067746620 cites W1993201779 @default.
• W3067746620 cites W1998093640 @default.
• W3067746620 cites W1998367993 @default.
• W3067746620 cites W2002288024 @default.
• W3067746620 cites W2005392755 @default.
• W3067746620 cites W2006304581 @default.
• W3067746620 cites W2012604733 @default.
• W3067746620 cites W2013306140 @default.
• W3067746620 cites W2014425795 @default.
• W3067746620 cites W2017361929 @default.
• W3067746620 cites W2022948355 @default.
• W3067746620 cites W2026418335 @default.
• W3067746620 cites W2026961081 @default.
• W3067746620 cites W2028477895 @default.
• W3067746620 cites W2029667189 @default.
• W3067746620 cites W2030319745 @default.
• W3067746620 cites W2036502774 @default.
• W3067746620 cites W2040858214 @default.
• W3067746620 cites W2040934203 @default.
• W3067746620 cites W2041000185 @default.
• W3067746620 cites W2043502580 @default.
• W3067746620 cites W2044626483 @default.
• W3067746620 cites W2044882887 @default.
• W3067746620 cites W2048822589 @default.
• W3067746620 cites W2055956723 @default.
• W3067746620 cites W2056245019 @default.
• W3067746620 cites W2057621608 @default.
• W3067746620 cites W2058493522 @default.
• W3067746620 cites W2067204014 @default.
• W3067746620 cites W2070359441 @default.
• W3067746620 cites W2079064092 @default.
• W3067746620 cites W2085519055 @default.
• W3067746620 cites W2097152121 @default.
• W3067746620 cites W2097412382 @default.
• W3067746620 cites W2105632084 @default.
• W3067746620 cites W2107349404 @default.
• W3067746620 cites W2109837376 @default.
• W3067746620 cites W2130616267 @default.
• W3067746620 cites W2133131542 @default.
• W3067746620 cites W2139543085 @default.
• W3067746620 cites W2141109380 @default.
• W3067746620 cites W2144562104 @default.
• W3067746620 cites W2147850116 @default.
• W3067746620 cites W2151550848 @default.
• W3067746620 cites W2159275700 @default.
• W3067746620 cites W2163291301 @default.
• W3067746620 cites W2180739100 @default.
• W3067746620 cites W2260414198 @default.
• W3067746620 cites W2295059836 @default.
• W3067746620 cites W2330989754 @default.
• W3067746620 cites W2335585438 @default.
• W3067746620 cites W2467129931 @default.
• W3067746620 cites W2486597359 @default.
• W3067746620 cites W2520728390 @default.
• W3067746620 cites W2528162531 @default.
• W3067746620 cites W2543120616 @default.
• W3067746620 cites W2552299231 @default.
• W3067746620 cites W2613669786 @default.
• W3067746620 cites W2755908776 @default.
• W3067746620 cites W2907580401 @default.
• W3067746620 cites W2912566673 @default.
• W3067746620 cites W2976142053 @default.
• W3067746620 cites W46148605 @default.
• W3067746620 cites W938283201 @default.
• W3067746620 doi "https://doi.org/10.1016/j.crstbi.2020.08.001" @default.
• W3067746620 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8244415" @default.
• W3067746620 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34235478" @default.
• W3067746620 hasPublicationYear "2020" @default.
• W3067746620 type Work @default.
• W3067746620 sameAs 3067746620 @default.
• W3067746620 citedByCount "3" @default.
• W3067746620 countsByYear W30677466202022 @default.
• W3067746620 countsByYear W30677466202023 @default.
• W3067746620 crossrefType "journal-article" @default.
• W3067746620 hasAuthorship W3067746620A5015471381 @default.
• W3067746620 hasAuthorship W3067746620A5034743915 @default.
• W3067746620 hasAuthorship W3067746620A5056115805 @default.
• W3067746620 hasBestOaLocation W30677466201 @default.
• W3067746620 hasConcept C104317684 @default.
• W3067746620 hasConcept C116569031 @default.
• W3067746620 hasConcept C121332964 @default.

• next