Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912402646> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W2912402646 endingPage "64a" @default.
- W2912402646 startingPage "63a" @default.
- W2912402646 abstract "The assembly of hetero-tetrameric HbA is a multi-faceted pathway emphasized by both quaternary structure formations via the interacting alpha and beta subunits of HbA as well as the oxygen coordinating heme (Fe(II)-protoporphyrin IX) insertion within the heme cavity of each subunit. Folding transition states at different stages of this pathway could act as precursors for misassembly of HbA, leading to hemoglobinopathies and disruption of oxygen transport within the cardiovascular system. Simultaneous circular dichroism and visible absorbance measurements of guanidine hydrochloride induced unfolding of HbA showed that the initial formation of the alpha-beta dimer interface occurs via a molten globule heterodimer state with ∼30% helical content. Reversible hemin (Fe(III)-protoporphyrin IX) binding to the melted heme pockets in this transition state results in a six coordinate, low spin iron state known as a hemichrome, which stabilizes the hetero-dimer interface. Atomic level modeling of hemin disassociation from native HbA using the Amber 2018 molecular dynamics (MD) package showed that these hemichrome transition states can also occur in both the folded alpha and beta subunits at 37 °C via hexacoordination of the iron by internal histidines within the heme cavity. These atomic level simulations enable us to characterize the transitionary nature of bond breaking and formation with metal cofactors that is beyond the resolution limits of solution spectroscopy and X-ray crystallography. Modeling studies involving thermodynamics integration are also currently being undertaken to measure free energy change for HbA tetramer interface formation, which markedly enhances heme affinity of HbA." @default.
- W2912402646 created "2019-02-21" @default.
- W2912402646 creator A5014694160 @default.
- W2912402646 creator A5017318009 @default.
- W2912402646 creator A5029596891 @default.
- W2912402646 creator A5070293533 @default.
- W2912402646 date "2019-02-01" @default.
- W2912402646 modified "2023-09-29" @default.
- W2912402646 title "Resolving the Transition States of Human Hemoglobin Assembly through a Combination of Spectroscopic Studies and All-Atom Molecular Dynamics Simulations" @default.
- W2912402646 doi "https://doi.org/10.1016/j.bpj.2018.11.388" @default.
- W2912402646 hasPublicationYear "2019" @default.
- W2912402646 type Work @default.
- W2912402646 sameAs 2912402646 @default.
- W2912402646 citedByCount "0" @default.
- W2912402646 crossrefType "journal-article" @default.
- W2912402646 hasAuthorship W2912402646A5014694160 @default.
- W2912402646 hasAuthorship W2912402646A5017318009 @default.
- W2912402646 hasAuthorship W2912402646A5029596891 @default.
- W2912402646 hasAuthorship W2912402646A5070293533 @default.
- W2912402646 hasBestOaLocation W29124026461 @default.
- W2912402646 hasConcept C104292427 @default.
- W2912402646 hasConcept C104317684 @default.
- W2912402646 hasConcept C125996951 @default.
- W2912402646 hasConcept C133571119 @default.
- W2912402646 hasConcept C166014724 @default.
- W2912402646 hasConcept C178790620 @default.
- W2912402646 hasConcept C181199279 @default.
- W2912402646 hasConcept C185592680 @default.
- W2912402646 hasConcept C20705724 @default.
- W2912402646 hasConcept C2776217839 @default.
- W2912402646 hasConcept C2776403692 @default.
- W2912402646 hasConcept C2777723881 @default.
- W2912402646 hasConcept C2778886173 @default.
- W2912402646 hasConcept C2778917026 @default.
- W2912402646 hasConcept C2779480358 @default.
- W2912402646 hasConcept C2779546866 @default.
- W2912402646 hasConcept C55493867 @default.
- W2912402646 hasConcept C75473681 @default.
- W2912402646 hasConcept C7927669 @default.
- W2912402646 hasConcept C8010536 @default.
- W2912402646 hasConceptScore W2912402646C104292427 @default.
- W2912402646 hasConceptScore W2912402646C104317684 @default.
- W2912402646 hasConceptScore W2912402646C125996951 @default.
- W2912402646 hasConceptScore W2912402646C133571119 @default.
- W2912402646 hasConceptScore W2912402646C166014724 @default.
- W2912402646 hasConceptScore W2912402646C178790620 @default.
- W2912402646 hasConceptScore W2912402646C181199279 @default.
- W2912402646 hasConceptScore W2912402646C185592680 @default.
- W2912402646 hasConceptScore W2912402646C20705724 @default.
- W2912402646 hasConceptScore W2912402646C2776217839 @default.
- W2912402646 hasConceptScore W2912402646C2776403692 @default.
- W2912402646 hasConceptScore W2912402646C2777723881 @default.
- W2912402646 hasConceptScore W2912402646C2778886173 @default.
- W2912402646 hasConceptScore W2912402646C2778917026 @default.
- W2912402646 hasConceptScore W2912402646C2779480358 @default.
- W2912402646 hasConceptScore W2912402646C2779546866 @default.
- W2912402646 hasConceptScore W2912402646C55493867 @default.
- W2912402646 hasConceptScore W2912402646C75473681 @default.
- W2912402646 hasConceptScore W2912402646C7927669 @default.
- W2912402646 hasConceptScore W2912402646C8010536 @default.
- W2912402646 hasIssue "3" @default.
- W2912402646 hasLocation W29124026461 @default.
- W2912402646 hasOpenAccess W2912402646 @default.
- W2912402646 hasPrimaryLocation W29124026461 @default.
- W2912402646 hasRelatedWork W1505502736 @default.
- W2912402646 hasRelatedWork W1593238473 @default.
- W2912402646 hasRelatedWork W1978054475 @default.
- W2912402646 hasRelatedWork W1999522939 @default.
- W2912402646 hasRelatedWork W2015572850 @default.
- W2912402646 hasRelatedWork W2143694555 @default.
- W2912402646 hasRelatedWork W2218056722 @default.
- W2912402646 hasRelatedWork W2949256646 @default.
- W2912402646 hasRelatedWork W957695923 @default.
- W2912402646 hasRelatedWork W2048356567 @default.
- W2912402646 hasVolume "116" @default.
- W2912402646 isParatext "false" @default.
- W2912402646 isRetracted "false" @default.
- W2912402646 magId "2912402646" @default.
- W2912402646 workType "article" @default.