NDLI: Computational study of coagulation factor VIIa’s affinity for phospholipid membranes

Content Provider	Springer Nature Link
Author	Taboureau, Olivier Olsen, Ole Hvilsted
Copyright Year	2006
Abstract	The interaction between the γ-carboxyglutamic acid-rich domain of coagulation factor VIIa (FVIIa), a vitamin-K-dependent enzyme, and phospholipid membranes plays a major role in initiation of blood coagulation. However, despite a high sequence and structural similarity to the Gla domain of other vitamin-K-dependent enzymes with a high membrane affinity, its affinity for negatively charged phospholipids is poor. A few amino acid differences are responsible for this observation. Based on the X-ray structure of lysophosphatidylserine (lysoPS) bound to the Gla domain of bovine prothrombin (Prth), models of the Gla domain of wildtype FVIIa and mutated FVIIa Gla domains in complex with lysoPS were built. Molecular dynamics (MD) and steered molecular dynamics (SMD) simulations on the complexes were applied to investigate the significant difference in the binding affinity. The MD simulation approach provides a structural and dynamic support to the role of P10Q and K32E mutations in the improvement of the membrane contact. Hence, rotation of the Gly11 main chain generated during the MD simulation results in a hydrogen bond with Q10 side chain as well as the appearance of a hydrogen bond between E32 and Q10 forcing the loop harbouring Arg9 and Arg15 to shrink and thereby enhances the accessibility of the phospholipids to the calcium ions. Furthermore, the application of the SMD simulation method to dissociate C6-lysoPS from a series of Gla domain models exhibits a ranking of the rupture force that can be useful in the interpretation of the PS interaction with Gla domains. Finally, adiabatic mapping of Gla6 residue in FVIIa with or without insertion of Tyr4 confirms the critical role of the insertion on the conformation of the side chain Gla6 in FVIIa and the corresponding Gla7 in Prth.
Starting Page	133
Ending Page	144
Page Count	12
File Format	PDF
ISSN	01757571
Journal	European Biophysics Journal
Volume Number	36
Issue Number	2
e-ISSN	14321017
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-11-28
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Coagulation factor FVIIa Gla domain Lysophosphatidylserine Membrane binding Steered molecular dynamics Molecular dynamics Neurobiology Animal Physiology Plant Physiology Biochemistry Cell Biology Biophysics/Biomedical Physics
Content Type	Text
Resource Type	Article
Subject	Medicine Biophysics

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Molecular dynamics simulations and membrane protein structure quality

Biomimetic tethered lipid membranes designed for membrane-protein interaction studies

Ligand-escape pathways from the ligand-binding domain of PPARγ receptor as probed by molecular dynamics simulations

Novel methods for preparing phospholipid coated microbubbles

Steered molecular dynamics simulations of ligand–receptor interaction in lipocalins

Metals and membranes in neuroscience

Acetyl-[Asn30,Tyr32]-calcitonin fragment 8-32 forms channels in phospholipid planar lipid membranes

Metal effects on the membrane interactions of amyloid-β peptides

A molecular dynamics study of the bee venom melittin in aqueous solution, in methanol, and inserted in a phospholipid bilayer

Computational study of coagulation factor VIIa’s affinity for phospholipid membranes

Similar Documents

Molecular dynamics simulations and membrane protein structure quality

Biomimetic tethered lipid membranes designed for membrane-protein interaction studies

Ligand-escape pathways from the ligand-binding domain of PPARγ receptor as probed by molecular dynamics simulations

Novel methods for preparing phospholipid coated microbubbles

Steered molecular dynamics simulations of ligand–receptor interaction in lipocalins

Metals and membranes in neuroscience

Acetyl-[Asn30,Tyr32]-calcitonin fragment 8-32 forms channels in phospholipid planar lipid membranes

Metal effects on the membrane interactions of amyloid-β peptides

A molecular dynamics study of the bee venom melittin in aqueous solution, in methanol, and inserted in a phospholipid bilayer

Computational study of coagulation factor VIIa’s affinity for phospholipid membranes