Protein domain class

Eortunately, a 3D model does not have to be absolutely perfect to be helpful in biology, as demonstrated by the applications listed above. However, the type of question that can be addressed with a particular model does depend on the model s accuracy. At the low end of the accuracy spectrum, there are models that are based on less than 25% sequence identity and have sometimes less than 50% of their atoms within 3.5 A of their correct positions. However, such models still have the correct fold, and even knowing only the fold of a protein is frequently sufficient to predict its approximate biochemical function. More specifically, only nine out of 80 fold families known in 1994 contained proteins (domains) that were not in the same functional class, although 32% of all protein structures belonged to one of the nine superfolds [229]. Models in this low range of accuracy combined with model evaluation can be used for confirming or rejecting a match between remotely related proteins [9,58]. 

Two types of SORs have been firstly described by Lombard et al. [44] and Jenney et al. [45]. The first one is a small protein called desulfoferrodoxin (Dfx) found in anaerobic sulfate-reducing bacteria Desulfoarculus baarsii containing two protein domains iron center I and iron center II [44]. Iron center II is supposed to be responsible for the superoxide reducing activity. Another SOR has been isolated from anerobic archaea, Pyrococcus furiosus, which has a unique mononuclear iron center [45], Lombard et al. [46] and Jovanovic et al. [47] also demonstrated that the Treponema pallidum protein of T. pallidum belongs to a new class of SORs. 

A class of DUBs only identified since 2002 is the OTU (ovarian tumor protein) DUB class. The OTU domain was originally identified in an ovarian tumor protein from Drosophila mdanogaster, and over 100 proteins from organisms ranging from bacteria to humans are annotated as having an OTU domain. The members of this protein superfamily were annotated as cysteine proteases, but no specific function had been demonstrated for any of these proteins. The first hint of a role for OTU proteins in the ubiquitin pathway was afforded by the observation that an OTU-domain-containing protein, HSPC263, reacted with ubiquitin vinyl sulfone (an active-site-directed irreversible inhibitor of DUBs) [41]. 

Finally, it should be mentioned that there are a number of protein domains that have some structural resemblance to ubiquitin, although a sequence similarity cannot be established - not even by the most sophisticated methods available today. It cannot be excluded that there are true instances of convergent evolution among these cases. However, it appears more likely that these proteins and domains represent distant members of the ubiquitin superfamily, which have undergone a fundamental change of function and no longer need to conserve sequence positions that are considered hallmarks of ubiquitin-like molecules. In particular three domain classes should be mentioned in this context. The PERM domain (4.1, ezrin,... 

Each synthetase module contains three active site domains The A domain catalyzes activation of the amino acid (or hydroxyacid) by formation of an aminoacyl- or hydroxyacyl-adenylate, just as occurs with aminoacyl-tRNA synthetases. However, in three-dimensional structure the A domains do not resemble either of the classes of aminoacyl-tRNA synthetases but are similar to luciferyl adenylate (Eq. 23-46) and acyl-CoA synthetases.11 The T-domain or peptidyl carrier protein domain resembles the acyl carrier domains of fatty acid and polyketide synthetases in containing bound phos-phopantetheine (Fig. 14-1). Its -SH group, like the CCA-terminal ribosyl -OH group of a tRNA, displaces AMP, transferring the activated amino acid or hydroxy acid to the thiol sulfur of phosphopan-tetheine. The C-domain catalyzes condensation (peptidyl transfer). The first or initiation module lacks a C-domain, and the final termination module contains an extra termination domain. The process parallels that outlined in Fig. 21-11.1... 

Plants also produce structurally related enzymes (chitinases) that catalyse the hydrolysis of chitin (Table 12.2) and hence damage chitin-based insect integuments. Class I chitinases are basic enzymes with an jV-terminal hevein-related CBD and vacuole-targeting C-terminal signals whereas Class II enzymes are acidic proteins lacking these CBD and vacuole-targeting domains. Class IV chitinases are variously basic and acidic extracellular proteins with... 

Figure 33.33. Class II MHC Protein. A class IIMHC protein consists of homologous a and P chains, each of which has an amino-terminal domain that constitutes half of the peptide-binding structure, as well as a carboxyl-terminal immunoglobulin domain. The peptide-binding site is similar to that in class I MHC proteins except that it is open at both ends, allowing class II MHC proteins to bind longer peptides than those bound by class I.

Molecular replacement (see Rossmann, 1972) has another very useful application, one that has for the most part superseded that described above for directly deducing phase information from noncrystallographic relationships. It derives from the tendency of macromolecules to fall into classes with shared structural motifs, in that they are homologous and often evolutionarily related. Macromolecules of similar function from different species often share structural features and are frequently almost identical. Viruses of the same or similar families do as well. Protein domains of common occurrence may serve as modules to be assembled in different combinations to make a variety of proteins having redundant structural features. 

Figure 13.1. Structural classes of protein folds, showing how the folds can be classified into different structural classes. Top row the three basic fold classes a, containing only a helices a and p, containing a helices and p sheets and p, containing only p sheets. Middle row three different architectural subclasses of the a and p class triosephosphate isomerase (TIM) barrel, three-layer sandwich, and roll. Bottom row two different arrangements of the "three-layer sandwich . The spiral conformations are the a helices, and the broad arrows are the p sheets. (From Orengo, C. A., Michie, A. D., Jones, S. et al. [1997]. CATH - a hierarchic classification of protein domain structures [Figure 2]. Structure, 5, 1093-108. Copyright 1997, Elsevier Science. Reprinted with permission.)...

Figure 5-2. Typical conservation patterns of three protein classes. Residues invariant or conserved in more than 80% ofthe sequences are printed on a black or grey background, respectively. A Mainly nonpolar conservation in the UBA domain, a small protein domain that interacts preferentially with ubiquitin1781. B Invariant polar active site residues in the phospholipase D family1291. C Nearly invariant metal-binding residues in the HtpX/Ste24 family of Zn-containing metalloproteases.

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