Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen.


Abstract

The Fab portion of a humanized antibody (Fab-12; IgG form known as rhuMAb VEGF) to vascular endothelial growth factor (VEGF) has been affinity-matured through complementarity-determining region (CDR) mutation, followed by affinity selection using monovalent phage display. After stringent binding selections at 37 degrees C, with dissociation (off-rate) selection periods of several days, high affinity variants were isolated from CDR-H1, H2, and H3 libraries. Mutations were combined to obtain cumulatively tighter-binding variants. The final variant identified here, Y0317, contained six mutations from the parental antibody. In vitro cell-based assays show that four mutations yielded an improvement of about 100-fold in potency for inhibition of VEGF-dependent cell proliferation by this variant, consistent with the equilibrium binding constant determined from kinetics experiments at 37 degrees C. Using X-ray crystallography, we determined a high-resolution structure of the complex between VEGF and the affinity-matured Fab fragment. The overall features of the binding interface seen previously with wild-type are preserved, and many contact residues are maintained in precise alignment in the superimposed structures. However, locally, we see evidence for improved contacts between antibody and antigen, and two mutations result in increased van der Waals contact and improved hydrogen bonding. Site-directed mutants confirm that the most favorable improvements as judged by examination of the complex structure, in fact, have the greatest impact on free energy of binding. In general, the final antibody has improved affinity for several VEGF variants as compared with the parental antibody; however, some contact residues on VEGF differ in their contribution to the energetics of Fab binding. The results show that small changes even in a large protein-protein binding interface can have significant effects on the energetics of interaction.

Submission Details

ID: kGTbL7D64

Submitter: Shu-Ching Ou

Submission Date: Feb. 22, 2019, 1:32 p.m.

Version: 1

Publication Details
Chen Y;Wiesmann C;Fuh G;Li B;Christinger HW;McKay P;de Vos AM;Lowman HB,J Mol Biol (1999) Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. PMID:10543973
Additional Information

ΔΔG values were reported in AB-Bind article: (DOI: 10.1002/pro.2829)

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1KMX 2002-07-24 Heparin-binding Domain from Vascular Endothelial Growth Factor
2VGH 1998-04-08 HEPARIN-BINDING DOMAIN FROM VASCULAR ENDOTHELIAL GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE
2RCJ 2008-01-22 Solution structure of human Immunoglobulin M
1VGH 1998-04-08 HEPARIN-BINDING DOMAIN FROM VASCULAR ENDOTHELIAL GROWTH FACTOR, NMR, 20 STRUCTURES
1KAT 2002-11-02 Solution Structure of a Phage-Derived Peptide Antagonist in Complex with Vascular Endothelial Growth Factor
4LLD 2014-01-29 1.19 Structure of wild-type IgG1 antibody heavy chain constant domain 1 and light chain lambda constant domain (IgG1 CH1:Clambda) at 1.19A
3TV3 2011-10-19 1.29 Crystal structure of broad and potent HIV-1 neutralizing antibody PGT128 in complex with Man9
1MKK 2002-12-11 1.32 Disulfide deficient mutant of vascular endothelial growth factor A (C61A and C104A)
4LLQ 2014-01-29 1.42 Structure of redesigned IgG1 first constant and lambda domains (CH1:Clambda constant redesign 2 beta, CRD2b) at 1.42A
5HSF 2016-02-03 1.52 1.52 Angstrom Crystal Structure of Fc fragment of Human IgG1.
4GLS 2012-09-05 1.6 Crystal Structure of Chemically Synthesized Heterochiral {D-Protein Antagonist plus VEGF-A} Protein Complex in space group P21
4NWU 2014-10-22 1.6 Crystal structure of APE1551, an anti-human NGF Fab with a nine amino acid insertion in CDR H1
4GLN 2012-09-05 1.6 Crystal Structure of Chemically Synthesized Heterochiral {D-Protein Antagonist plus VEGF-A} Protein Complex in space group P21/n
5EWI 2016-11-23 1.6 Crystal Structure of the Human Fab VRC38.01, an HIV-1 V1V2-Directed Neutralizing Antibody Isolated from Donor N90
3TWC 2011-10-19 1.65 Crystal structure of broad and potent HIV-1 neutralizing antibody PGT127 in complex with Man9
1L6X 2002-04-10 1.65 FC FRAGMENT OF RITUXIMAB BOUND TO A MINIMIZED VERSION OF THE B-DOMAIN FROM PROTEIN A CALLED Z34C
5JIH 2017-04-12 1.66 Crystal structure of HER2 binding IgG1-Fc (Fcab STAB19)
1FLT 1999-01-13 1.7 VEGF IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR
5U66 2017-05-24 1.7 Modified single helix from the B-domain of protein A bound to IgG1 Fc
3MCL 2010-11-24 1.7 Anti-beta-amyloid antibody c706 fab in space group P21
4KZN 2014-06-04 1.71 crystal structure of human VEGF-A receptor binding domain
4NWT 2014-10-22 1.75 Crystal structure of the anti-human NGF Fab APE1531
4BSV 2013-08-21 1.75 Heterodimeric Fc Antibody Azymetric Variant 1
3DJ9 2008-09-16 1.75 Crystal Structure of an isolated, unglycosylated antibody CH2 domain
4LLM 2014-01-29 1.75 Structure of redesigned IgG1 first constant and lambda domains (CH1:Clambda constant redesign 1, CRD1) at 1.75A
4XMP 2015-04-29 1.78 Crystal structure of broadly and potently neutralizing antibody VRC08 in complex with HIV-1 clade A strain Q842.d12 gp120
5JII 2017-04-12 1.79 Crystal structure of human IgG1-Fc
1N0X 2004-04-13 1.8 Crystal Structure of a Broadly Neutralizing Anti-HIV-1 Antibody in Complex with a Peptide Mimotope
4QAF 2015-05-06 1.8 Crystal structure of an engineered lipocalin (Anticalin) in complex with VEGF(8-109)
3UPA 2012-06-20 1.8 A general strategy for the generation of human antibody variable domains with increased aggregation resistance
4W4O 2015-04-29 1.8 High-resolution crystal structure of Fc bound to its human receptor Fc-gamma-RI
4W4N 2015-04-29 1.8 Crystal structure of human Fc at 1.80 A
5W38 2017-10-18 1.8 1.80A resolution structure of human IgG3 Fc (N392K)
5HYF 2017-02-01 1.8 Glycosylated Knob-Knob Fc fragment (P6122)
3X12 2014-12-24 1.8 Crystal structure of HLA-B*57:01.I80N
1N7M 2003-02-04 1.8 Germline 7G12 with N-methylmesoporphyrin
3VH8 2011-10-26 1.8 KIR3DL1 in complex with HLA-B*5701
4B53 2012-12-05 1.8 Crystal structure of the isolated IgG4 CH3 domain
5JIK 2017-04-12 1.82 Crystal structure of HER2 binding IgG1-Fc (Fcab H10-03-6)
1AQK 1998-02-04 1.84 THREE-DIMENSIONAL STRUCTURE OF A HUMAN FAB WITH HIGH AFFINITY FOR TETANUS TOXOID
5W5N 2017-09-13 1.85 Crystal structure of human IgG4-Sigma2 Fc fragment
3QTK 2011-07-27 1.85 The crystal structure of chemically synthesized VEGF-A
5GSQ 2017-06-28 1.85 Crystal structure of IgG Fc with a homogeneous glycoform and Antibody-Dependent Cellular Cytotoxicity
4O4Y 2014-03-26 1.85 Crystal structure of the anti-hinge rabbit antibody 2095-2 in complex with IDES hinge peptide
6G1E 2019-04-10 1.88 BEAT Fc with improved heterodimerization (Q3A-D84.4Q)
5HYE 2017-02-01 1.89 Glycosylated Knob-Knob Fc fragment (P212121)
4KU1 2014-02-19 1.9 Role of the hinge and C-gamma-2/C-gamma-3 interface in immunoglobin G1 Fc domain motions: implications for Fc engineering
5DVL 2016-03-30 1.9 Fc Design 20.8.37 A chain homodimer Y349S/T366M/K370Y/K409V
5DJZ 2016-03-30 1.9 Fc Heterodimer Design 7.8 D399M/Y407A + T366V/K409V
4WI2 2015-09-30 1.9 Structural mapping of the human IgG1 binding site for FcRn: hu3S193 Fc (wild-type)
6DCV 2018-06-06 1.9 Crystal structure of human anti-tau antibody CBTAU-27.1
4C54 2013-11-13 1.9 Crystal structure of recombinant human IgG4 Fc
5W5M 2017-09-13 1.9 Crystal structure of human IgG4-Sigma1 Fc fragment
1VPP 1999-02-23 1.9 COMPLEX BETWEEN VEGF AND A RECEPTOR BLOCKING PEPTIDE
5DI8 2016-03-30 1.9 Fc Knob-Hole Heterodimer T366W + T366S/L368A/Y407V
4WI7 2015-09-30 1.9 Structural mapping of the human IgG1 binding site for FcRn: hu3S193 Fc mutation H435A
4J12 2013-05-01 1.9 monomeric Fc
3D85 2008-09-02 1.9 Crystal structure of IL-23 in complex with neutralizing FAB
4DZ8 2012-08-01 1.91 human IgG1 Fc fragment Heterodimer
2VPF 1998-07-29 1.93 VASCULAR ENDOTHELIAL GROWTH FACTOR REFINED TO 1.93 ANGSTROMS RESOLUTION
5U52 2017-05-24 1.94 2 helix minimized version of the B-domain from Protein A (Z34C0 bound to IgG1 Fc (monoclinic form)
4BM7 2013-07-03 1.95 Crystal Structure of IgG Fc F241A mutant with native glycosylation
5HVW 2016-08-17 1.95 Monomeric IgG4 Fc
5DN2 2016-07-20 1.95 Human NRP2 b1 domain in complex with the peptide corresponding to the C-terminus of VEGF-A
1GAF 1996-07-11 1.95 48G7 HYBRIDOMA LINE FAB COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID
5M3V 2017-05-10 1.97 BEAT Fc
4EOW 2012-08-22 1.97 Crystal structure of a disease-associated anti-human GM-CSF autoantibody MB007
3QCU 2011-03-30 1.98 Crystal structure of the LT3015 antibody Fab fragment in complex with lysophosphatidic acid (14:0)
3U0W 2012-10-03 2.0 AD related murine antibody Fragment
6DCW 2018-06-06 2.0 Crystal structure of human anti-tau antibody CBTAU-27.1 Fab in complex with a human tau peptide
1D6V 2000-02-09 2.0 CONFORMATION EFFECTS IN BIOLOGICAL CATALYSIS INTRODUCED BY OXY-COPE ANTIBODY MATURATION
3AVE 2011-04-06 2.0 Crystal Structure of the Fucosylated Fc Fragment from Human Immunoglobulin G1
3WUW 2014-05-28 2.0 KIR3DL1 in complex with HLA-B*57:01.I80T
5DJ6 2016-03-30 2.0 Fc Heterodimer Design 6.1 F405W/Y407A + T366M
1D5I 2000-02-09 2.0 UNLIGANDED GERMLINE PRECURSOR OF AN OXY-COPE CATALYTIC ANTIBODY
1VGE 1996-06-10 2.0 TR1.9 FAB FRAGMENT OF A HUMAN IGG1 KAPPA AUTOANTIBODY
3V7M 2012-02-22 2.02 Crystal structure of monoclonal human anti-Rhesus D Fc IgG1 T125(YB2/0) in the presence of Zn2+
5IW3 2017-03-29 2.05 anti-CD20 monoclonal antibody Fc fragment
3RU8 2011-11-02 2.07 Structure of an HIV epitope scaffold in complex with neutralizing antibody b12 Fab
1MJV 2002-12-11 2.1 DISULFIDE DEFICIENT MUTANT OF VASCULAR ENDOTHELIAL GROWTH FACTOR A (C51A and C60A)
5DJC 2016-03-30 2.1 Fc Heterodimer Design 8.1 L368V/Y407A + T366V/K409F
1AJ7 1997-11-12 2.1 IMMUNOGLOBULIN 48G7 GERMLINE FAB ANTIBODY COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID. AFFINITY MATURATION OF AN ESTEROLYTIC ANTIBODY
5HHC 2016-03-09 2.1 Crystal Structure of Chemically Synthesized Heterochiral {RFX037 plus VEGF-A} Protein Complex in space group P21/n
2RCS 1997-11-12 2.1 IMMUNOGLOBULIN 48G7 GERMLINE FAB-AFFINITY MATURATION OF AN ESTEROLYTIC ANTIBODY
4NQT 2014-03-12 2.1 anti-parallel Fc-hole(T366S/L368A/Y407V) homodimer
5HHD 2016-03-09 2.1 Crystal Structure of Chemically Synthesized Heterochiral {RFX037 plus VEGF-A} Protein Complex in space group P21
1A4J 1998-05-13 2.1 DIELS ALDER CATALYTIC ANTIBODY GERMLINE PRECURSOR
5DJY 2016-03-30 2.15 Fc Heterodimer Design 20.8 Y349S/T366V/K370Y/K409V + E357D/S364Q/Y407A
5O4E 2017-08-30 2.15 Crystal structure of VEGF in complex with heterodimeric Fcab JanusCT6
4BSW 2013-08-21 2.15 Heterodimeric Fc Antibody Azymetric Variant 2
3X11 2014-12-24 2.15 Crystal structure of HLA-B*57:01.I80N.L82R.R83G
3AGV 2010-11-10 2.15 Crystal structure of a human IgG-aptamer complex
3QCT 2011-03-30 2.15 Crystal structure of the humanized apo LT3015 anti-lysophosphatidic acid antibody Fab fragment
4Q74 2014-07-23 2.19 F241A Fc
4HIX 2013-03-13 2.2 Crystal structure of a humanised 3D6 Fab bound to amyloid beta peptide
3AY4 2011-08-03 2.2 Crystal structure of nonfucosylated Fc complexed with bis-glycosylated soluble form of Fc gamma receptor IIIa
2DTS 2007-03-13 2.2 Crystal Structure of the Defucosylated Fc Fragment from Human Immunoglobulin G1
4O51 2014-03-26 2.2 Crystal structure of the QAA variant of anti-hinge rabbit antibody 2095-2 in complex with IDES hinge peptide
4WI6 2015-09-30 2.2 Structural mapping of the human IgG1 binding site for FcRn: hu3S193 Fc mutation N434A
3SGJ 2011-08-03 2.2 Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgIII and antibodies lacking core fucose
5DJX 2016-03-30 2.25 Fc Heterodimer Design 2.9 L368M/K370E + E357A/S364G
4ZNC 2015-07-15 2.28 Fc fragment of human IgG in complex with the C domain of staphylococcal protein A mutant - Q9W
5DJ0 2016-03-30 2.28 Fc Heterodimer Design 11.2 Y349S/K370Y + E357D/S364Q
3C2S 2008-08-19 2.3 Structural Characterization of a Human Fc Fragment Engineered for Lack of Effector Functions
6F2Z 2018-12-12 2.3 Structure of a Fc mutatnt
4CDH 2014-11-12 2.3 Crystallographic structure of the Human Igg1 alpha 2-6 sialilated Fc-Fragment
5B38 2016-03-30 2.3 KIR3DL1*005 in complex with HLA-B*57:01
2NY7 2007-02-06 2.3 HIV-1 gp120 Envelope Glycoprotein Complexed with the Broadly Neutralizing CD4-Binding-Site Antibody b12
3D6G 2009-06-16 2.3 Fc fragment of IgG1 (Herceptin) with protein-A mimetic peptide dendrimer ligand.
5DJD 2016-03-30 2.3 Fc Heterodimer Design 5.1 T366V + Y407F
1I7Z 2001-08-08 2.3 ANTIBODY GNC92H2 BOUND TO LIGAND
1OQO 2003-03-20 2.3 Complex between G0 version of an Fc bound to a minimized version of Protein A called Mini-Z
4BYH 2013-08-21 2.3 Crystal structure of sialylated IgG Fc
4XNY 2015-04-29 2.3 Crystal structure of broadly and potently neutralizing antibody VRC08C in complex with HIV-1 clade A strain Q842.d12 gp120
5DK0 2016-03-30 2.3 Fc Heterodimer Design 20.8.34 Y349S/T366M/K370Y/K409V + E356G/E357D/S364Q/Y407A
5V43 2017-06-21 2.32 Engineered human IgG Fc domain aglyco801
5IW6 2017-03-29 2.34 anti-CD20 monoclonal antibody Fc fragment
4Q7D 2014-07-23 2.35 Wild type Fc (wtFc)
2IWG 2007-03-27 2.35 COMPLEX BETWEEN THE PRYSPRY DOMAIN OF TRIM21 AND IGG FC
4C55 2013-11-13 2.35 Crystal structure of serum-derived human IgG4 Fc
4B7I 2012-10-17 2.36 Crystal Structure of Human IgG Fc Bearing Hybrid-type Glycans
5D4Q 2016-02-10 2.39 Crystal structure of GASDALIE IgG1 Fc
6D58 2019-05-15 2.39 Crystal structure of a Fc fragment of Human IgG3
3SGK 2011-08-03 2.4 Unique carbohydrate/carbohydrate interactions are required for high affinity binding of FcgIII and antibodies lacking core fucose
5DJ8 2016-03-30 2.4 Fc Heterodimer Design 7.7 D399M/Y407A + T366V/K409I
1BJ1 1999-01-13 2.4 VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH A NEUTRALIZING ANTIBODY
1H3T 2003-01-23 2.4 Crystal structure of the human igg1 fc-fragment,glycoform (mn2f)2
1H3U 2003-01-23 2.4 CRYSTAL STRUCTURE OF THE HUMAN IGG1 FC-FRAGMENT,GLYCOFORM (M3N2F)2
1A4K 1998-05-13 2.4 DIELS ALDER CATALYTIC ANTIBODY WITH TRANSITION STATE ANALOGUE
1CZ8 2000-03-20 2.4 VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH AN AFFINITY MATURED ANTIBODY
4XXD 2015-04-29 2.41 Crystal Structure of mid-region amyloid beta capture by solanezumab
3P9W 2012-04-18 2.41 Crystal structure of an engineered human autonomous VH Domain in complex with VEGF
4ZNE 2015-11-11 2.42 IgG1 Fc-FcgammaRI ecd complex
1H3X 2003-11-20 2.44 CRYSTAL STRUCTURE OF THE HUMAN IGG1 FC-FRAGMENT,GLYCOFORM (G0F)2
5K64 2017-09-06 2.44 Crystal structure of VEGF binding IgG1-Fc (Fcab 448)
6AXP 2017-12-13 2.48 Structure of cetuximab with aminoheptanoic acid-linked n-octylarginine meditope variant
6AU5 2017-12-13 2.48 Structure of cetuximab with aminoheptanoic acid-linked n-butylarginine meditope variant
6AYN 2017-12-13 2.48 Structure of cetuximab with aminoheptanoic acid-linked N-(3-aminopropyl)-L-arginine meditope variant
6AZK 2017-12-13 2.48 Structure of cetuximab with aminoheptanoic acid-linked N-(3-hydroxypropyl)-L-arginine meditope variant
6AZL 2017-12-13 2.48 Structure of cetuximab with aminoheptanoic acid-linked N-carboxyethylarginine meditope variant
4ACP 2012-04-25 2.49 Deactivation of human IgG1 Fc by endoglycosidase treatment
1UCB 1997-03-12 2.5 STRUCTURE OF UNCOMPLEXED FAB COMPARED TO COMPLEX (1CLY, 1CLZ)
5DVN 2016-03-30 2.5 Fc K392D/K409D homodimer
1MKG 2002-12-11 2.5 DISULFIDE DEFICIENT MUTANT OF VASCULAR ENDOTHELIAL GROWTH FACTOR A (C57A and C102A)
4NQU 2014-03-12 2.5 anti-parallel Fc-knob (T366W) homodimer
2RFX 2008-07-08 2.5 Crystal Structure of HLA-B*5701, presenting the self peptide, LSSPVTKSF
4X98 2015-06-03 2.5 Immunoglobulin Fc heterodimer variant
3DO3 2009-07-21 2.5 Human 1gG1 Fc fragment, 2.5 Angstrom structure
4X99 2015-06-03 2.5 Immunoglobulin Fc heterodimers variant
1CLY 1996-08-01 2.5 IGG FAB (HUMAN IGG1, KAPPA) CHIMERIC FRAGMENT (CBR96) COMPLEXED WITH LEWIS Y NONOATE METHYL ESTER
5DVO 2016-03-30 2.5 Fc K392D/K409D homodimer
5B39 2016-03-30 2.5 KIR3DL1*015 in complex with HLA-B*57:01
1VPF 1998-04-08 2.5 STRUCTURE OF HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR
1PG7 2003-08-26 2.5 Murine 6A6 Fab in complex with humanized anti-Tissue Factor D3H44 Fab
5K65 2017-09-06 2.5 Crystal structure of VEGF binding IgG1-Fc (Fcab CT6)
5U4Y 2017-05-17 2.5 IgG Fc bound to 3 helix of the B-domain from Protein A
3FJT 2009-03-24 2.5 Crystal structure of a human Fc fragment engineered for extended serum half-life
2WAH 2009-03-10 2.51 Crystal Structure of an IgG1 Fc Glycoform (Man9GlcNAc2)
3QCV 2011-03-30 2.51 Crystal structure of the LT3015 antibody Fab fragment in complex with lysophosphatidic acid (18:2)
2QL1 2008-04-01 2.53 Structural Characterization of a Mutated, ADCC-Enhanced Human Fc Fragment
6BFT 2018-10-31 2.55 Structure of Bevacizumab Fab mutant in complex with VEGF
3S1K 2011-08-17 2.55 The Development of Peptide-based Tools for the Analysis of Angiogenesis
5DJ2 2016-03-30 2.56 Fc Heterodimer Design 7.4 Y407A + T366V/K409V
1TZH 2004-08-31 2.6 Crystal Structure of the Fab YADS1 Complexed with h-VEGF
1MIM 1997-05-15 2.6 IGG FAB FRAGMENT (CD25-BINDING)
1AXS 1998-02-04 2.6 MATURE OXY-COPE CATALYTIC ANTIBODY WITH HAPTEN
3U7W 2011-11-16 2.6 Crystal structure of NIH45-46 Fab
1OQX 2003-03-25 2.6 G-2 glycovariant of human IgG Fc bound to minimized version of Protein A called Z34C
3WJJ 2013-11-13 2.6 Crystal structure of IIb selective Fc variant, Fc(P238D), in complex with FcgRIIb
5DVK 2016-03-30 2.6 Fc Design 7.7 B chain homodimer T366V/K409I
5DK2 2016-03-30 2.6 Fc Heterodimer E356K/D399K + K392D/K409D
3BDY 2008-11-18 2.6 Dual specific bH1 Fab in complex with VEGF
4D3C 2016-01-13 2.62 Crystal structure of the NK1 domain of HGF in complex with anti-HGF monoclonal antibody SFN68.
4NQS 2014-03-12 2.64 Knob-into-hole IgG Fc
4NM4 2013-12-25 2.65 Crystal structure of broadly neutralizing antibody CR8043
4DEQ 2012-02-08 2.65 Structure of the Neuropilin-1/VEGF-A complex
4WI9 2015-09-30 2.65 Structural mapping of the human IgG1 binding site for FcRn: hu3S193 Fc mutation I253A/H310A
1HKL 1997-03-12 2.68 FREE AND LIGANDED FORM OF AN ESTEROLYTIC CATALYTIC ANTIBODY
1HEZ 2001-08-10 2.7 antibody-antigen complex
1DN2 2000-05-17 2.7 FC FRAGMENT OF HUMAN IGG1 IN COMPLEX WITH AN ENGINEERED 13 RESIDUE PEPTIDE DCAWHLGELVWCT-NH2
1DFB 1993-10-31 2.7 STRUCTURE OF A HUMAN MONOCLONAL ANTIBODY FAB FRAGMENT AGAINST GP41 OF HUMAN IMMUNODEFICIENCY VIRUS TYPE I
5LG1 2016-12-14 2.7 Room temperature structure of human IgG4-Fc from crystals analysed in situ
5HY9 2017-02-01 2.7 Glycosylated, disulfide-linked Knob-into-Hole Fc fragment
5TPS 2017-10-25 2.7 Structure of a Fc heterodimer
1QTY 2000-01-12 2.7 VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR
5FV1 2016-02-17 2.7 Crystal structure of hVEGF in complex with VK domain antibody
3V95 2012-02-22 2.7 Crystal structure of monoclonal human anti-rhesus D Fc and IgG1 t125(yb2/0) in the presence of EDTA
1HZH 2001-08-15 2.7 CRYSTAL STRUCTURE OF THE INTACT HUMAN IGG B12 WITH BROAD AND POTENT ACTIVITY AGAINST PRIMARY HIV-1 ISOLATES: A TEMPLATE FOR HIV VACCINE DESIGN
4WI3 2015-09-30 2.7 Structural mapping of the human IgG1 binding site for FcRn: hu3S193 Fc mutation I253A
4YDV 2015-08-12 2.7 STRUCTURE OF THE ANTIBODY 7B2 THAT CAPTURES HIV-1 VIRIONS
4D2N 2014-07-02 2.7 Crystal structure of deglycosylated serum-derived human IgG4 Fc
4ZFF 2015-07-01 2.75 Dual-acting Fab 5A12 in complex with VEGF
3V8C 2012-02-22 2.77 Crystal structure of monoclonal human anti-rhesus D Fc IgG1 t125(yb2/0) double mutant (H310 and H435 in K)
3WN5 2014-11-19 2.78 Crystal structure of asymmetrically engineered Fc variant in complex with FcgRIIIa
2FJG 2006-02-07 2.8 Structure of the G6 Fab, a phage derived Fab fragment, in complex with VEGF
3O11 2010-09-08 2.8 Anti-beta-amyloid antibody c706 fab in space group c2
1TZI 2004-08-31 2.8 Crystal Structure of the Fab YADS2 Complexed with h-VEGF
4WI5 2015-09-30 2.8 Structural mapping of the human IgG1 binding site for FcRn: hu3S193 Fc mutation H310A
1D5B 2000-02-09 2.8 UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY
4WI4 2015-09-30 2.8 Structural mapping of the human IgG1 binding site for FcRn: hu3S193 Fc mutation S254A
1F6L 2002-10-23 2.8 VARIABLE LIGHT CHAIN DIMER OF ANTI-FERRITIN ANTIBODY
4WI8 2015-09-30 2.8 Structural mapping of the human IgG1 binding site for FcRn: hu3S193 Fc mutation Y436A
1FC2 1981-10-02 2.8 Crystallographic Refinement and Atomic Models of a Human FC Fragment and its Complex with Fragment B of Protein A from Staphylococcus Aureus at 2.9-and 2.8-Angstroms Resolution
3DNK 2009-07-21 2.84 Enzyme deglycosylated Human IgG1 Fc fragment
1H3W 2003-01-23 2.85 Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity
3WJL 2013-11-13 2.86 Crystal structure of IIb selective Fc variant, Fc(V12), in complex with FcgRIIb
3IU3 2010-01-26 2.9 Crystal structure of the Fab fragment of therapeutic antibody Basiliximab in complex with IL-2Ra (CD25) ectodomain
3WKN 2014-10-29 2.9 Crystal structure of the artificial protein AFFinger p17 (AF.p17) complexed with Fc fragment of human IgG
3S1B 2011-08-17 2.9 The Development of Peptide-based Tools for the Analysis of Angiogenesis
5HYI 2017-02-01 2.9 Glycosylated, disulfide-linked Hole-Hole Fc fragment
1FC1 1981-10-02 2.9 CRYSTALLOGRAPHIC REFINEMENT AND ATOMIC MODELS OF A HUMAN FC FRAGMENT AND ITS COMPLEX WITH FRAGMENT B OF PROTEIN A FROM STAPHYLOCOCCUS AUREUS AT 2.9-AND 2.8-ANGSTROMS RESOLUTION
5DJA 2016-03-30 2.9 Fc Heterodimer Design 9.1 Y407M + T366I
5DVM 2016-03-30 2.95 Fc Design 20.8.37 B chain homodimer E357D/S364R/Y407A
1T83 2004-09-28 3.0 CRYSTAL STRUCTURE OF A HUMAN TYPE III FC GAMMA RECEPTOR IN COMPLEX WITH AN FC FRAGMENT OF IGG1 (ORTHORHOMBIC)
2J6E 2007-04-10 3.0 Crystal Structure of an Autoimmune Complex between a Human IgM Rheumatoid Factor and IgG1 Fc reveals a Novel Fc Epitope and Evidence for Affinity Maturation
4Q6Y 2014-07-23 3.0 Crystal structure of a chemoenzymatic glycoengineered disialylated Fc (di-sFc)
5BW7 2015-10-14 3.0 Crystal structure of nonfucosylated Fc Y296W mutant complexed with bis-glycosylated soluble form of Fc gamma receptor IIIa
6D3O 2019-04-24 3.1 Crystal Structure of Vascular Endothelial Growth Factor (VEGF8-109) with HH4, an alpha/beta-Peptide with Irregular Secondary Structure
2FJH 2006-02-07 3.1 Structure of the B20-4 Fab, a phage derived Fab fragment, in complex with VEGF
1H3V 2003-01-23 3.1 CRYSTAL STRUCTURE OF THE HUMAN IGG1 FC-FRAGMENT,GLYCOFORM (G2F)2,SG P212121
1BBJ 1994-01-31 3.1 CRYSTAL STRUCTURE OF A CHIMERIC FAB' FRAGMENT OF AN ANTIBODY BINDING TUMOUR CELLS
3EO1 2008-12-02 3.1 Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3
4WPB 2015-04-15 3.11 Vascular endothelial growth factor in complex with alpha/beta-VEGF-1
5D6D 2016-02-10 3.13 Crystal structure of GASDALIE IgG1 Fc in complex with FcgRIIIa
3S7G 2012-05-30 3.13 Aglycosylated human igg1 fc fragment
1ADQ 1998-09-16 3.15 CRYSTAL STRUCTURE OF A HUMAN IGM RHEUMATOID FACTOR FAB IN COMPLEX WITH ITS AUTOANTIGEN IGG FC
3V2A 2012-01-18 3.2 VEGFR-2/VEGF-A COMPLEX STRUCTURE
1E4K 2000-08-06 3.2 CRYSTAL STRUCTURE OF SOLUBLE HUMAN IGG1 FC FRAGMENT-FC-GAMMA RECEPTOR III COMPLEX
1FCC 1995-04-20 3.2 CRYSTAL STRUCTURE OF THE C2 FRAGMENT OF STREPTOCOCCAL PROTEIN G IN COMPLEX WITH THE FC DOMAIN OF HUMAN IGG
5V4E 2017-06-21 3.22 Engineered human IgG Fc domain glyco801 (Fc801)
3TYG 2011-10-19 3.25 Crystal structure of broad and potent HIV-1 neutralizing antibody PGT128 in complex with a glycosylated engineered gp120 outer domain with miniV3 (eODmV3)
5K33 2017-04-12 3.3 Crystal structure of extracellular domain of HER2 in complex with Fcab STAB19
4XNZ 2015-04-29 3.39 Crystal structure of broadly and potently neutralizing antibody VRC06B in complex with HIV-1 clade A/E strain 93TH057 gp120
5FV2 2016-02-17 3.45 Crystal structure of hVEGF in complex with VH domain antibody
4X4M 2015-04-08 3.48 Structure of FcgammaRI in complex with Fc reveals the importance of glycan recognition for high affinity IgG binding
2QR0 2007-08-14 3.5 Structure of VEGF complexed to a Fab containing TYR and SER in the CDRs
1T89 2004-09-14 3.5 CRYSTAL STRUCTURE OF A HUMAN TYPE III FC GAMMA RECEPTOR IN COMPLEX WITH AN FC FRAGMENT OF IGG1 (HEXAGONAL)
3RY6 2011-08-31 3.8 Complex of fcgammariia (CD32) and the FC of human IGG1
4N0U 2014-02-05 3.8 Ternary complex between Neonatal Fc receptor, serum albumin and Fc
4NM8 2013-12-25 4.0 Crystal structure of broadly neutralizing antibody CR8043 bound to H3 influenza hemagglutinin
5T89 2017-02-01 4.0 Crystal structure of VEGF-A in complex with VEGFR-1 domains D1-6
1H3Y 2003-01-23 4.1 Crystal structure of a human IgG1 Fc-fragment,high salt condition
6DE7 2018-06-06 4.12 Crystal Structure at 4.3 A Resolution of Glycosylated HIV-1 Clade A BG505 SOSIP.664 Prefusion Env Trimer with Interdomain Stabilization 113C-429GCG in Complex with Broadly Neutralizing Antibodies PGT122 and 35O22
5K8D 2017-06-14 4.19 Crystal structure of rFVIIIFc
5KWG 2017-04-12 4.3 Crystal structure of extracellular domain of HER2 in complex with Fcab H10-03-6
2GJ7 2006-05-30 5.0 Crystal Structure of a gE-gI/Fc complex

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
200.0 H,K Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A P01857 IGHG1_HUMAN
181.8 H,K Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A P01860 IGHG3_HUMAN
182.2 H,K Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A P01861 IGHG4_HUMAN
200.0 J,L Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A P01834 IGKC_HUMAN
183.0 J,L Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A P01597 KV139_HUMAN
183.0 J,L Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A P04432 KVD39_HUMAN
200.0 V,W Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A P15692 VEGFA_HUMAN
195.8 V,W Fab fragment,Vascular endothelial growth factor A P49151 VEGFA_PIG
187.2 V,W Fab fragment,Vascular endothelial growth factor A P15691 VEGFA_BOVIN
185.2 V,W Fab fragment,Vascular endothelial growth factor A P50412 VEGFA_SHEEP
189.8 V,W Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A Q9GKR0 VEGFA_HORSE
193.4 V,W Fab fragment, heavy chain,Fab fragment, light chain,Vascular endothelial growth factor A Q9MYV3 VEGFA_CANLF
187.0 V,W Fab fragment,Vascular endothelial growth factor A P26617 VEGFA_CAVPO
180.8 V,W Fab fragment,Vascular endothelial growth factor A Q99PS1 VEGFA_MESAU
183.0 V,W Fab fragment,Vascular endothelial growth factor A Q00731 VEGFA_MOUSE
183.0 V,W Fab fragment,Vascular endothelial growth factor A P16612 VEGFA_RAT