COMPARISON OF LOW OXIDOREDUCTION POTENTIAL CYTOCHROME C553 FROM DESULFOVIBRIO-VULGARIS WITH THE CLASS-I CYTOCHROME-C FAMILY

The cytochrome c553 from Desulfovibrio vulgaris (DvH c553) is of impor tance in the understanding of the relationship of structure and functi on of cytochrome c due to its lack of sequence homology with other cyt ochromes, and its abnormally low oxide-reduction potential. In evoluti onary terms, this protein also represents an important reference point for the understanding of both bacterial and mitochondrial cytochromes c. Using the recently determined nuclear magnetic resonance (NMR) str ucture of the reduced protein we compare the structural, dynamic, and functional characteristics of DvH c553 with members of both the mitoch ondrial and bacterial cytochromes c to characterize the protein in the context of the cytochrome c family, and to understand better the cont rol of oxide-reduction potential in electron transfer proteins. Despit e the low sequence homology, striking structural similarities between this protein and representatives of both eukaryotic [cytochrome c from tuna (tuna c)] and prokaryotic [Pseudomonas aeruginosa c551 (Psa c551 )] cytochromes c have been recognized. The previously observed helical core is also found in the DvH c553. The structural framework and hydr ogen bonding network of the DvH c553 is most similar to that of the tu na c, with the exception of an insertion loop of 24 residues closing t he heme pocket and protecting the propionates, which is absent in the DvH c553. In contrast, the Psa c551 protects the propionates from the solvent principally by extending the methionine Ligand arm. The electr ostatic distribution at the recognized encounter surface around the he me in the mitochondrial cytochrome is reproduced in the DvH c553, and corresponding hydrogen bonding networks, particularly in the vicinity of the heme cleft, exist in both molecules. Thus, although the cytochr ome DvH c553 exhibits higher primary sequence homology to other bacter ial cytochromes c, the structural and physical homology is significant ly greater with respect to the mitochondrial cytochrome c. The major s tructural and functional difference is the absence of solvent protecti on for the heme, differentiating this cytochrome from both reference c ytochromes, which have evolved different mechanisms to cover the propi onates. This suggests that the abnormal redox potential of the DvH c55 3 is linked to the raised accessibility of the heme and supports the t heory that redox potential in cytochromes is controlled by heme propio nate solvent accessibility. (C) 1996 Wiley-Liss, Inc.