Domains structural comparison

Crane et al. first established the three-dimensional fold of NOS by solving the structure of a monomeric form of the mouse iNOS heme domain (78). This version of iNOS was missing the first 114 residues, which are known to be critical for dimer formation and activity (79). The monomer structure was soon followed by the dimeric heme domain structures of mouse iNOS (80), bovine eNOS (81), and the human isoforms of iNOS (82, 83) and eNOS (82). A comparison of eNOS and iNOS reveals that the structures are essentially the same with an overall root-mean-square deviation in backbone atoms of 1.1 A (S3). The sequence identity between human iNOS and bovine eNOS is 60% for 420 residues compared in the crystal structures (83). 

Labesse, G. et al., Structural comparisons lead to the definition of a new superfamily of NAD(P)(H)-accepting oxidoreductases the single-domain reductases/epimerases/dehydrogenases (the RED family). Biochem. J., 304, 95, 1994. 

Banuelos, S., Saraste, M., and Carugo, K. D. (1998). Structural comparisons of calponin homology domains Implications for actin binding. Structure 6, 1419-1431. 

Structural comparison among 18 different TRAF2 trimers and 6 TRAF3 trimers revealed that the trimeric structure is highly conserved. However, slight variations in the relative disposition of the protomers in the TRAF domain trimer are observed. These structural differences are exemplified by a flexing of the head of the mushroom relative to the stalk, on the order of 2-6° (Fig. 3D) and are unlikely to have functional implications. The coiled coil domains are more flexible, especially near the ends remote to the TRAF-C domains. 

A comparison of the different variants of the jS-barrel domain structure in Fig. 1 shows that domain 1 of ascorbate oxidase has the simplest /3-barrel with only two four-stranded /8-sheets. Plastocyanin and azurin are quite similar but between strands 4 (El) and 6 (FI) they have insertions of one strand (plastocyanin) or one strand and an a-helix (azurin). Domain 2 has one additional strand H2 in sheet D next to strand E2 (sheet B and strand El in domain 1) and two additional strands, F2 and G2, in sheet C next to strand 12 (sheet A and strand FI in domain 1). Domain 3 resembles domain 2 except for the insertion of the short a-helices and the addition of the four-stranded /8-sheet at its N terminus. 

The similarity matrix calculated in Messerschmidt and Huber (202) indicates clearly the six-domain structure of ceruloplasmin and three-domain structures for laccase and ascorbate oxidase. The internal triplication within the ceruloplasmin amino-acid sequence is reflected by values of about 60% difference. Comparison of both the N-terminal domains and the C-terminal domains of the blue oxidases indicates, respectively, a relationship that is closer and relevant values for percent difference that are significantly lower than those for other comparisons. This might reflect the requirements for the trinuclear copper site. The lowest values of about 70 to 73% difference are observed for both N-terminal and C-terminal domains of laccase and ascorbate oxidase, showing that the two oxidases are more closely related to ceruloplasmin than either of them. 

To analyze the subtle specific structural features of thermophilic archaeal proteins, comparisons with closely related mesophilic proteins are necessary. Since the Crenarchaeota comprise exclusively thermophilic strains, respective comparisons are only possible with proteins from Euryarchaeota. Structural comparisons between thermophilic archaeal proteins and mesophilic bacterial or eucaryal proteins are unlikely to be useful because of the large evolutionary distance between different domains, which blur the thermoadaptive features. 

Figure 2. Comparison of domain structures of representative invertebrate coronins. From the left side, abbreviations indicating organisms, protein names, domain structures and amino acid numbers for each protein are given. All coronin proteins visualized in this figure have also been included into the comprehensive and meticulous phylogeny tree of coronins presented in chapter 4. D, Dictyostelium discoideum FH, Homo sapiens W, Caenorhabditis elegans F, Drosophila melanogaster (Shina MC, Noegel AA unpublished).

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