GLORIA — GEOMAR Library Ocean Research Information Access

Hits per page

hits 1 - 2 | 2 hits

Sorting

Electronic Resource

Crystallization and preliminary X-ray analysis of W120K mutant of streptavidin (2001)

Pazy, Yael ; Laitinen, Olli H. ; Ravoy, Bilha ; [et al.]

Copenhagen : International Union of Crystallography (IUCr)

Acta crystallographica 57 (2001), S. 1885-1886

add to mindlist on the mindlist

Details

ISSN: 1399-0047

Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001

Topics: Chemistry and Pharmacology , Geosciences , Physics

Notes: Bacterial streptavidin and chicken avidin are homotetrameric proteins that share an exceptionally high affinity towards the vitamin biotin. The biotin-binding sites in both proteins contain a crucial tryptophan residue contributed from an adjacent subunit. This particular tryptophan (W110 in avidin and W120 in streptavidin) plays an important role in both biotin binding and in the quaternary stabilities of the proteins. An intriguing naturally occurring alteration of tryptophan to lysine was previously described in the C-terminal domain of sea-urchin fibropellins, which share a relatively high sequence similarity with avidin and streptavidin. Avidin (Avm-W110K) and streptavidin (Savm-W120K) mutations show substantially reduced affinities towards biotin as well as the dissociation of their tetrameric structure into stable avidin and streptavidin dimers. Savm-W120K was crystallized at 293 K using the hanging-drop vapour-diffusion method. The crystals diffract to 1.7 Å resolution using synchrotron radiation and belong to the monoclinic space group P21, with unit-cell parameters a = 50.43, b = 100.41, c = 52.51 Å, β = 112.12°. The asymmetric unit contains four molecules of Savm-W120K, with a corresponding VM of 2.3 Å3 Da−1 and a solvent content of 46%.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1107/S0907444901015141

Permalink

	Location	Call Number	Limitation	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

Electronic Resource

Inhibition of tumor growth by poly(ethylene glycol) derivatives of anti-ErbB2 antibodies (2000)

Hurwitz, Esther ; Klapper, Leah N. ; Wilchek, Meir ; [et al.]

Springer

Cancer immunology immunotherapy 49 (2000), S. 226-234

add to mindlist on the mindlist

Details

ISSN: 1432-0851

Keywords: Key words Anti-ErbB2 ; PEG ; Tumor ; Fab′

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract Poly(ethylene glycol) (PEG) modification of substances with antitumor activity was shown to enhance penetration into growing solid tumors and extend antitumor effects. Accordingly, PEG was introduced as a modifier to two types of monoclonal antibodies (N12 and L26) specific to the ErbB2 (HER2) oncoprotein. These antibodies suppress the growth of tumors overexpressing ErbB2 (e.g. N87 human tumor) and the effect of PEG on their antitumor activity was evaluated. Methoxy-PEG-maleimide conjugated to sulfhydryl groups at the hinge region of the antibodies impaired their antibody binding to N87 tumor cells and did not enhance the antitumor inhibitory activity in tumor-bearing mice. A branched N-hydroxysuccinimide-activated PEG (PEG2), conjugated through amino groups of the protein, was used for binding to the whole antibody (Ab) or to its monomeric Fab′ fragment. When tested against N87 cells in vitro, the binding activity and antitumor cytotoxic effects of Ab-PEG2 were mostly preserved. PEG2 modification did not seem to alter the tumor-inhibitory activity of the antibodies in vivo and the same pattern of tumor development was observed during the first few weeks following administration. However, the stimulating effects of PEG were observed at later stages of tumor growth since tumor development was either slowed down or completely arrested. Furthermore, a second tumor implanted into the same mice during this later stage was significantly or completely inhibited, as compared to results in mice injected with the unmodified antibody. The Fab′-PEG2 monomeric derivative was also shown to be effective in inhibiting the growth of a second tumor. The extended and prolonged enhancing effect of PEG on the antitumor activity of antibodies or Fab′ fragments directed against ErbB2 may be of importance in the treatment of ErbB2-overexpressing neoplasms.