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Purification and crystallization of complexes modeling the active state of the fragile histidine triad protein
Journal article   Open access

Purification and crystallization of complexes modeling the active state of the fragile histidine triad protein

Charles Brenner, Helen C Pace, Carlo M Croce, Kay Huebner, Preston N Garrison, Angela K Robinson, Larry D Barnes, Angelika Rosler, Xiao Hai Liu and G. Michael Blackburn
Protein Engineering, Vol.10(12), pp.1461-1463
1997
DOI: 10.1093/protein/10.12.1461
PMID: 9543008
url
https://doi.org/10.1093/protein/10.12.1461View
Published (Version of record) Open Access

Abstract

Fragile histidine triad protein (Fhit) is a diadenosine triphosphate (ApppA) hydrolase encoded at the human chromosome 3 fragile site which is frequently disrupted in tumors. Reintroduction of FHIT coding sequences to cancer cell lines with FHIT deletions suppressed the ability of these cell lines to form tumors in nude mice even when the reintroduced FHIT gene had been mutated to allow ApppA binding but not hydrolysis. Because this suggested that the tumor suppressor activity of Fhit protein depends on substrate-dependent signaling rather than ApppA catabolism, we prepared two crystalline forms of Fhit protein that are expected to model its biologically active, substrate-bound state. Wild-type and the His96Asn forms of Fhit were overexpressed in Escherichia coli, purified to homogeneity and crystallized in the presence and absence of ApppA and an ApppA analog. Single crystals obtained by vapor diffusion against ammonium sulfate diffracted X-rays to beyond 2.75 A resolution. High quality native synchrotron X-ray data were collected for an orthorhombic and a hexagonal crystal form.

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