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Titolo:
Structural effects of framework mutations on a humanized anti-lysozyme antibody
Autore:
Holmes, MA; Buss, TN; Foote, J;
Indirizzi:
Fred Hutchinson Canc Res Ctr, Program Mol Med, Seattle, WA 98109 USA Fred Hutchinson Canc Res Ctr Seattle WA USA 98109 , Seattle, WA 98109 USA Univ Washington, Dept Immunol, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 Dept Immunol, Seattle, WA 98195 USA
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 1, volume: 167, anno: 2001,
pagine: 296 - 301
SICI:
0022-1767(20010701)167:1<296:SEOFMO>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
RESHAPING HUMAN-ANTIBODIES; HYPERVARIABLE LOOPS; FAB FRAGMENT; BINDING-SITE; PROTEINS; CONFORMATION; RESOLUTION; COMPLEX; COMPLEMENTARITY; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Foote, J Fred Hutchinson Canc Res Ctr, Program Mol Med, 1100 Fairview Ave N,C3-168,POB 19024, Seattle, WA 98109 USA Fred Hutchinson Canc Res Ctr 1100Fairview Ave N,C3-168,POB 19024 Seattle WA USA 98109
Citazione:
M.A. Holmes et al., "Structural effects of framework mutations on a humanized anti-lysozyme antibody", J IMMUNOL, 167(1), 2001, pp. 296-301

Abstract

A humanized version of the mouse anti-lysozyme Ab D1.3 was previously constructed as an Fv fragment and its structure was crystallographically determined in the free form and in complex with lysozyme. Here we report five newcrystal structures of single-amino acid substitution mutants of the humanized Fv fragment, four of which were determined as Fv-lysozyme complexes. The crystals were isomorphous with the parent forms, and were refined to freeR values of 28-31 % at resolutions of 2.7-2.9 Angstrom. Residue 27 in other Abs has been implicated in stabilizing the conformation of the first complementarity-determining region (CDR) of the H chain, residues 31-35. We find that a Phe-to-Ser mutation at 27 alters the conformation of immediately adjacent residues, but this change is only weakly transmitted to Ag binding residues in the nearby CDR. Residue 71 of the H chain has been proposed to control the relative disposition of H chain CDRs 1 and 2, based on the bulkof its side chain. However, in structures we determined with Val, Ala, or Arg substituted in place of Lys at position 71, no significant change in the conformation of CDRs 1 and 2 was observed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 00:24:23