Crystal structure analysis protein

This review presents an overview of the discovery of the Fepr protein, the spectroscopy that led to the suggestion that it contained a [6Fe-6S] cluster, and the subsequent crystal structure analysis that disproved this hypothesis, yet uncovered what is at a present a unique Fe-S cluster in biology. 

In mid-1997 an international conference took place in Santa Cruz, USA, in which, for the first time, the exclusive topic was structural aspects of RNA molecules. A report covering this meeting contains an impressive graphic which shows the RNA structures, RNA/DNA complexes, and RNA/protein complexes contained in the brookhaven database as a function of the year of their publication [29]. Between 1988 and 1993 there were just 20. However, in 1996 alone no less than 41 structures appeared. These new dimensions were headed by the crystal structural elucidation of the first larger RNA molecule since the first crystal structure of tRNA in 1973 [30], the 48 nucleotide long hammerhead ribo-zyme (HHR) [31-33]. This landmark achievement was followed by a crystal structure analysis of the P4-P6-domain of a group I intron [34-36] and, more recently, a crystal structure of the hepatitis delta virus ribozyme [37]. 

A quite new type of antibiotic and one of the few naturally-occurring boron compounds is boromycin (86). Hydrolytic cleavage of D-valine with the M(7) hydroxides gave caesium and rubidium salts of this antibiotic, and crystal structure analysis established the formula as (XIIT). The rubidium ion is irregularly coordinated by eight oxygen atoms. Experiments with models showed that the cation site would be the natural place for the—NH3+ end of the D-valine residue, and the whole structure raises the possibility that transport of larger alkali metals is related to the N-ends of peptides and proteins. 

The problem of phase determination is the fundamental one in any crystal structure analysis. Classically protein crystallography has depended on the method of multiple isomorphous replacement (MIR) in structure determination. However lack of strict isomorphism between the native and derivative crystals and the existence of multiple or disordered sites limit the resolution to which useful phases may be calculated. 

To date, complex proteins with biological activity (6), for use in X-ray crystal structure analysis (7) and ELISA systems (8), and for the development of animal drugs (9) have successfully been produced by using this system. Therefore, the Kaiko-baculovirus protein production system has broad applicability across the field of reverse chemical genetics for the analysis of protein function on the basis of interactions with chemical compounds. 

Amino acids of the general form, 1, are the monomeric molecules which are condensed to form the polypeptide chains of the fibrous and globular proteins. The naturally occurring molecules are the L-enantiomers, shown in 1 for chemical formulae see Fig. 19.1. D-amino acids can be synthesized and the individual L- or D-amino acids or the D,Lrracemates can be crystallized. All the common amino acids have been studied by neutron or X-ray crystal structure analysis (see Thble 14.1), in the anhydrous or hydrate forms, as hydrochlorides or hydrochloride hydrates. 

Figure 9.13. Analysis of the GRIND descriptors produced by the crystal structures ofthe proteins allowed us to find the distances between MIFs that could match GRIND descriptors 11-23 and 13-25. On the left are...

Lu Y, Wang R, Yang C-Y, Wang S. Analysis of hgand-bound water molecules in high-resoluhon crystal structures of protein-hgand complexes. J. Chem. Inf. Model. 2007 47 668-675. 

There are two cases that I felt most pleased about. One was the crystal structure analysis of an insect hemoglobin, in the late 1960s, when molecular evolution was not yet in evidence. It was a great surprise that an insect protein should have about the same structure as that of a mammalian protein. 

The extent of the diffraction pattern from a crystal is directly correlated with its degree of internal order. The more extensive the patterns, or the higher the resolution to which it extends, the more uniform are the molecules in the crystal and the more precise is their periodic arrangement. The level of detail to which atomic positions can be determined by a crystal structure analysis corresponds closely with the degree of crystalline order. While conventional molecular crystals often diffract almost to their theoretical limit of resolution, protein crystals, by comparison, are characterized by diffraction patterns of limited extent. 

Scharer, K., Morgenthaler, M., Paulini, R., Obst-Sander, U., Banner, D. W., Schlatter, D., Benz, J., Stihle, M., Diederich, F. Quantification of cation-pi interactions in protein-ligand complexes crystal-structure analysis of factor Xa bound to a quaternary anunonium ion ligand. Angew. Chem. Int. Ed. Engl. 2005, 44, 4400-4404. 

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