The most simple method currently used for solution of the macromolecular phase problem, single wavelength anomalous dispersion (SAD), still involves the incorporation of heavy atoms into protein crystals. After crystallization, finding such derivatives is the second major bottleneck in the determination of the 3D structure of bio-macromolecules.
Most labelling procedures focus on the protein itself in a "trial and error" fashion. Halogenated ATP and GTP analogs however, provide an alternative method that allows rational incorporation of heavy atoms into a large number of physiologically relevant enzymes:
Also check out our JBS Halo Kits → Crystallography & Cryo-EM, containing a selection of important Halo-ATP and Halo-GTP analogs!
Gruen et al. (1999) 2'-Halo-ATP and -GTP analogues: Rational phasing tools for protein crystallography. Protein Sci. 8:2524.
Gruen et al. (1999) Synthesis of 2'-iodo- and 2'-bromo-ATP and GTP analogues as potential phasing tools for X-ray crystallography. Nucleos. Nucleot. 18 (1):137.
Naber et al. (1995) A novel adenosine-triphosphate analog with a heavy-atom to target the nucleotide-binding site of proteins. Protein Sci. 4:1824.