Exceptions Proteins Containing Both Cysteines and Half Cystines

In the few proteins that have both cysteine and cystine residues, the cysteines are usually bonded, for example, 1CC5 (155C) cytochromes, in which two cysteines are bonded to the heme group, whereas the other two occur in disulfide bonds. Other examples include 2AZA, the electron transport protein azurin, in which the "free" cysteine is in the active site, forming a ligand to copper ion together with two histidines and a methionine, and 9PAP, the sulfhydryl proteinase papain, in which

28 A. Fiser, I. Simon, and G. J. Barton, FEBS Lett. 47,45 (1996).

29 V. I. Abkevich and E. I. Shakhnovich, J. Mol. Biol. 300, 975 (2000).

30 Z. Dosztanyi, A. Fiser, and I. Simon, J. Mol Biol. Ill, 597 (1997).

31 H. Nakashima and K. Nishikawa,./. Mol. Biol. 238, 54 (1994).

32 Z. Gugolya, Z. Dosztanyi, and I. Simon, Proteins 27, 360 (1997).

cysteine can be found in the active site. The only protein in our set that contains both the bonded and free forms of cysteine is 2SODB, which is an oxidoreductase (Cu,Zn-superoxide dismutase).33 In this molecule there are three cysteines, two of which Cys-144 and Cys-55 form a disulfide bond, whereas the third (Cys-6) is free.

The statistical correlations appear more pronounced if cysteines are grouped as bonded versus free rather than as cysteine versus cystine. This hypothesis was checked on a larger, less strictly selected data set (including lower resolution X-ray structures with a crystallographic R factor less than 25%). This larger set contained 233 proteins: 161 (69.1%) had only free cysteines, 24 (10.3%) had only half-cystines, 33 (14.2%) had neither, and 15 (6.4%) contained both forms of cysteine. By investigating this latter group, we found that at least half the proteins containing both cysteines and half-cystines occur in the same oxidation state, as in the cytochromes, sulfhydryl proteinases, and electron transport proteins cited above. This is true also for protein complexes such as endodeoxyribonuclease complex with actin (e.g., 1ATN). The actin forms a 1:1 complex with DNase I, with the actin having four sulfhydryl groups and the DNase having two disulfide bridges, but that situation corresponds to two separately folded molecules.

In the two data sets analyzed only a small percentage (2-4%) of the proteins contain both redox types of cysteines in the same molecule, but a specific role is often suspected for the free cysteines such as interdomain links, heavy atom-binding sites, and active sites. The number of cysteines in these proteins is not even.

0 0

Post a comment