Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Correlation between the binding affinity and the conformational entropy of nanobody SARS-CoV-2 spike protein complexes.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 119, Issue 31, Page e2205412119, Year 2022
Publish date	Aug 2, 2022
Authors	Halina Mikolajek / Miriam Weckener / Z Faidon Brotzakis / Jiandong Huo / Evmorfia V Dalietou / Audrey Le Bas / Pietro Sormanni / Peter J Harrison / Philip N Ward / Steven Truong / Lucile Moynie / Daniel K Clare / Maud Dumoux / Joshua Dormon / Chelsea Norman / Naveed Hussain / Vinod Vogirala / Raymond J Owens / Michele Vendruscolo / James H Naismith /
PubMed Abstract	Camelid single-domain antibodies, also known as nanobodies, can be readily isolated from naïve libraries for specific targets but often bind too weakly to their targets to be immediately useful. ...Camelid single-domain antibodies, also known as nanobodies, can be readily isolated from naïve libraries for specific targets but often bind too weakly to their targets to be immediately useful. Laboratory-based genetic engineering methods to enhance their affinity, termed maturation, can deliver useful reagents for different areas of biology and potentially medicine. Using the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and a naïve library, we generated closely related nanobodies with micromolar to nanomolar binding affinities. By analyzing the structure-activity relationship using X-ray crystallography, cryoelectron microscopy, and biophysical methods, we observed that higher conformational entropy losses in the formation of the spike protein-nanobody complex are associated with tighter binding. To investigate this, we generated structural ensembles of the different complexes from electron microscopy maps and correlated the conformational fluctuations with binding affinity. This insight guided the engineering of a nanobody with improved affinity for the spike protein.
External links	Proc Natl Acad Sci U S A / PubMed:35858383 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.55 - 4.2 Å
Structure data	14531 7z6v EMDB-14531, PDB-7z6v: CRYO-EM STRUCTURE OF SARS-COV-2 SPIKE : H11 nanobody complex Method: EM (single particle) / Resolution: 3.1 Å 14539 7z7x EMDB-14539, PDB-7z7x: CRYO-EM STRUCTURE OF SARS-COV-2 SPIKE : H11-H6 nanobody complex Method: EM (single particle) / Resolution: 3.3 Å 14543 7z85 EMDB-14543, PDB-7z85: CRYO-EM STRUCTURE OF SARS-COV-2 SPIKE : H11-B5 nanobody complex Method: EM (single particle) / Resolution: 3.1 Å 14544 7z86 EMDB-14544, PDB-7z86: CRYO-EM STRUCTURE OF SARS-COV-2 SPIKE : H11-H4 Q98R H100E nanobody complex in 1Up2Down conformation Method: EM (single particle) / Resolution: 3.4 Å 14575 7z9q EMDB-14575, PDB-7z9q: CRYO-EM STRUCTURE OF SARS-COV-2 SPIKE : H11-A10 nanobody complex Method: EM (single particle) / Resolution: 3.6 Å 14576 7z9r EMDB-14576, PDB-7z9r: CRYO-EM STRUCTURE OF SARS-COV-2 SPIKE : H11-H4 Q98R H100E nanobody complex in 2Up1Down conformation Method: EM (single particle) / Resolution: 4.2 Å PDB-7z1a: Nanobody H11 and F2 bound to RBD Method: X-RAY DIFFRACTION / Resolution: 2.59 Å PDB-7z1b: Nanobody H11-A10 and F2 bound to RBD Method: X-RAY DIFFRACTION / Resolution: 2.3 Å PDB-7z1c: Nanobody H11-B5 and H11-F2 bound to RBD Method: X-RAY DIFFRACTION / Resolution: 1.9 Å PDB-7z1d: Nanobody H11-H6 bound to RBD Method: X-RAY DIFFRACTION / Resolution: 1.55 Å PDB-7z1e: Nanobody H11-H4 Q98R H100E bound to RBD Method: X-RAY DIFFRACTION / Resolution: 1.59 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-HOH: WATER ChemComp-PEG: DI(HYDROXYETHYL)ETHER ChemComp-GOL: GLYCEROL ChemComp-NO3: NITRATE ION
Source	severe acute respiratory syndrome coronavirus 2 lama glama (llama) escherichia virus t4 tequatrovirus t4
Keywords	ANTIVIRAL PROTEIN / spike / nanobody / high affinity / Complex / Spike glycoprotein / nanobody H11 / nanobody H11-H6 / nanobody H11-B5 / nanobody H11-H4 Q98R H100E / nanobody H11-A10