CRYSTALLIZATION OF INTACT MONOCLONAL-ANTIBODIES

被引:47
作者
HARRIS, LJ
SKALETSKY, E
MCPHERSON, A
机构
[1] UNIV CALIF RIVERSIDE, DEPT BIOCHEM, RIVERSIDE, CA 92521 USA
[2] IMMUNOPHARMACEUT INC, SAN DIEGO, CA 92127 USA
关键词
IMMUNOGLOBULIN; IGG; INTACT ANTIBODY; CRYSTALLIZATION; X-RAY DIFFRACTION;
D O I
10.1002/prot.340230218
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Attempts were made to crystallize four monoclonal antibodies, one IgG(2a kappa) and three IgG(1 kappa). Using a PEG 3350 screen combined with detergents, and developed from our experiments with an IgG(2a kappa) antibody specific for canine lymphoma cells,(1,2) crystals have now been obtained of two of these four immunoglobulins, an antiphenytoin and an antiphenobarbital antibody. A complex between the antiphenobarbital antibody and its drug antigen crystallized as well. The antibody for phenytoin has, to this point, produced only clustered microcrystals, marginally suitable for X-ray analysis. Single crystals of the IgG(1 kappa) antibody against phenobarbital, however, were characterized by X-ray diffraction to be primitive monoclinic, with unit cell dimensions a = 67 Angstrom, b = 193 Angstrom, c = 74 Angstrom, and beta = 110 degrees. These crystals have an entire IgG(1 kappa) molecule as the asymmetric unit and they diffract to at least 3.2 Angstrom resolution. (C) 1995 Wiley-Liss, Inc.
引用
收藏
页码:285 / 289
页数:5
相关论文
共 21 条
[1]  
ALZARI PM, 1988, ANNU REV IMMUNOL, V6, P555
[2]  
COLMAN PM, 1988, ADV IMMUNOL, V43, P99
[3]   ANTIBODY STRUCTURE [J].
DAVIES, DR ;
CHACKO, S .
ACCOUNTS OF CHEMICAL RESEARCH, 1993, 26 (08) :421-427
[4]   ANTIBODY-ANTIGEN COMPLEXES [J].
DAVIES, DR ;
PADLAN, EA ;
SHERIFF, S .
ANNUAL REVIEW OF BIOCHEMISTRY, 1990, 59 :439-473
[5]  
EDMUNDSO.AB, 1970, J BIOL CHEM, V245, P2763
[6]   STRUCTURAL ASPECTS OF CONFORMATIONAL-CHANGES IN LIGAND-BINDING BY ANTIBODY FRAGMENTS [J].
EDMUNDSON, AB ;
GUDDAT, LW ;
SHAN, L ;
FAN, ZC ;
HANSON, BL .
RESEARCH IN IMMUNOLOGY, 1994, 145 (01) :56-61
[7]  
EDMUNDSON AB, 1993, IMMUNOMETHODS, V3, P197
[8]   MOBILE FC REGION IN ZIE IGG2 CRYOGLOBULIN - COMPARISON OF CRYSTALS OF F(AB')2 FRAGMENT AND INTACT IMMUNOGLOBULIN [J].
ELY, KR ;
COLMAN, PM ;
ABOLA, EE ;
HESS, AC ;
PEABODY, DS ;
PARR, DM ;
CONNELL, GE ;
LASCHINGER, CA ;
EDMUNDSON, AB .
BIOCHEMISTRY, 1978, 17 (05) :820-823
[9]   ANTIBODY-PRODUCTION BY HYBRIDOMAS [J].
GODING, JW .
JOURNAL OF IMMUNOLOGICAL METHODS, 1980, 39 :285-308
[10]   THE 3-DIMENSIONAL STRUCTURE OF AN INTACT MONOCLONAL-ANTIBODY FOR CANINE LYMPHOMA [J].
HARRIS, LJ ;
LARSON, SB ;
HASEL, KW ;
DAY, J ;
GREENWOOD, A ;
MCPHERSON, A .
NATURE, 1992, 360 (6402) :369-372