From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1dsf.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1dsf.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1dsf| PDB=1dsf | SCENE= }} | | {{STRUCTURE_1dsf| PDB=1dsf | SCENE= }} |
| | | | |
| - | '''THE CRYSTAL STRUCTURE OF THE DISULFIDE-STABILIZED FV FRAGMENT OF ANTICANCER ANTIBODY B1: CONFORMATIONAL INFLUENCE OF AN ENGINEERED DISULFIDE BOND'''
| + | ===THE CRYSTAL STRUCTURE OF THE DISULFIDE-STABILIZED FV FRAGMENT OF ANTICANCER ANTIBODY B1: CONFORMATIONAL INFLUENCE OF AN ENGINEERED DISULFIDE BOND=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | A recombinant Fv construct of the B1 monoclonal antibody that recognizes the LewisY-related carbohydrate epitope on human carcinoma cells has been prepared. The Fv is composed of the polypeptide chains of the VH and VL domains expressed independently and isolated as inclusion bodies. The Fv is prepared by combining and refolding equimolar amounts of guanidine chloride solubilized inclusion bodies. The Fv is stabilized by an engineered interchain disulfide bridge between residues VL100 and VH44. This construct has a similar binding affinity as that of the single-chain construct (Benhar and Pastan, Clin. Cancer Res. 1:1023-1029, 1995). The B1 disulfide-stabilized Fv (BldsFv) crystallizes in space group P6(1)22 with the unit cell parameters a = b = 80.1 A, and c = 138.1 A. The crystal structure of the BldsFv has been determined at 2.1-A resolution using the molecular replacement technique. The final structure has a crystallographic R-value of 0.187 with a root mean square deviation in bond distance of 0.014 A and in bond angle of 2.74 degrees. Comparisons of the BldsFv structure with known structures of Fv regions of other immunoglobulin fragments shows closely related secondary and tertiary structures. The antigen combining site of BldsFv is a deep depression 10-A wide and 17-A long with the walls of the depression composed of residues, many of which are tyrosines, from complementarity determining regions L1, L3, H1, H2, and H3. Model building studies indicate that the LewisY tetrasaccharide, Fuc-Gal-Nag-Fuc, can be accommodated in the antigen combining site in a manner consistent with the epitope predicted in earlier biochemical studies (Pastan, Lovelace, Gallo, Rutherford, Magnani, and Willingham, Cancer Res. 51:3781-3787, 1991). Thus, the engineered disulfide bridge appears to cause little, if any, distortion in the Fv structure, making it an effective substitute for the B1 Fab.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9593187}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9593187 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_9593187}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 27: |
Line 31: |
| | [[Category: Immunoglobulin]] | | [[Category: Immunoglobulin]] |
| | [[Category: Monoclonal antibody]] | | [[Category: Monoclonal antibody]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:13:11 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:32:52 2008'' |
Revision as of 20:32, 30 June 2008
Template:STRUCTURE 1dsf
THE CRYSTAL STRUCTURE OF THE DISULFIDE-STABILIZED FV FRAGMENT OF ANTICANCER ANTIBODY B1: CONFORMATIONAL INFLUENCE OF AN ENGINEERED DISULFIDE BOND
Template:ABSTRACT PUBMED 9593187
About this Structure
1DSF is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the disulfide-stabilized Fv fragment of anticancer antibody B1: conformational influence of an engineered disulfide bond., Almog O, Benhar I, Vasmatzis G, Tordova M, Lee B, Pastan I, Gilliland GL, Proteins. 1998 May 1;31(2):128-38. PMID:9593187
Page seeded by OCA on Mon Jun 30 23:32:52 2008
