Catalytic domain architecture

Protein kinases have a general architecture catalytic domain, a binding domain that orients the substrate to the catalytic site, and phosphate donor binding site which donates the y-phosphate to the acceptor hydroxyl residues. 

The colinearity of the modular architecture and the minimal catalytic domains within a module are observed in most multimodular PKSs known to date. However, there are several subclasses of PKSs that exhibit intriguing structural and biochemical features not observed among the best-known multimodular PKSs. 

FIGURE 57.13. Molecular architecture of bienzyme biosensor electrode containing tyrosinase and neuropathy target esterase catalytic domain (NEST). Reproduced with permission from Kohli et al. (2007a). 

The aaRSs can be divided evenly into two classes based on the architectures of their catalytic domains the presence of specific consensus sequences and their chemical properties (6). The catalytic core of Class I aaRSs is composed of a Rossmann dinucleotide binding fold that is marked by two signature consensus sequences KMSKS and HIGH (Fig. 2). Class II aaRSs are typically dimers or tetramers and possess a more unique catalytic core that is made up of seven antiparallel -strands flanked by a-helices. These enzymes have three consensus motifs (Fig. 2). Motif 1 [G4>XX4>xxP4>4>] is at the dimer interface, whereas motif 2 [FRXE-H/RXXXFXXX(D/E)] and motif 3 [G4>G4>G4>(D/E)R4>4>4>4>4>] are part of the active site (4>... 

Figure 3 Soluble guanylate cyclase, (a). Domain architecture of sCC. sGC consists of two homologous subunits, al and pi. Each subunit contains an N-terminal H-NOX domain, a central predicted PAS-like region, and a C-terminal catalytic domain. Heme (gray parallelogram) binds to the H-NOX domain on the pi subunit, (b). NO activation of sGC. NO binds to the sCC heme, which leads to the formation of a 5-coordinate ferrous nitrosyl complex and activates the protein several-hundred-fold above the basal level.

Several vital processes rely on clan PA peptidases. Chief among them are blood coagulation and the immune response, which involve cascades of sequential zymogen activation. In both systems, the chymotrypsin-fold peptidase domain is combined with one more associated protein domains, including apple, CUB, EGF, fibronectin, kringle, sushi, and von Willebrand factor domains. These protein domains are on the N-terminus as an extension of the propeptide segment of the peptidase. Such a trend of N-terminal-associated domains in the SIA peptidase family is common across all forms of life. The domain architecture pairs well with the zymogen activation mechanism, which liberates the proper N-terminus to enable catalytic activity. Often, the associated protein domains remain attached to... 

The fungal FAS is a large barrel-shaped protein with an extraordinarily complex architecture supported by many structural elements that constitute almost half of the entire molecule (Fig. 5A and B). The sides of the barrel are comprised of two trimeric P-chains, each chain containing four catalytic domains, acetyltransferase (AT), enoylreductase (ER),... 

Fig. 5. Architecture of the fungal FAS. (A) Structural overview of the barrel-shaped molecule showing the location of the equatorial wheel composed of the six alpha subunits flanked by two domes, each composed of a p subunit trimer. The barrel is 270 A long and 230 A wide at the equator. (B) Location of the structural underpinnings of the molecule with the catalytic domains removed. (C) Organization of the alpha-subunit hexamer. (D) Organization of one p-subunit trimer (adapted from Lomakin et al. [13] with permission). (See color plate section, plate no. 4.)...

Examples of tyrosine phosphatases that are subject to tyrosine phosphorylation include SHP-1 and SHP-2 [26]. These phosphatases are the SH2 domain containing tyrosine phosphatases that have the domain architecture shown and include two tandem N-terminal SH2 domains followed by a catalytic domain and ending in a C-terminal tyrosine phosphorylated tail (Fig. 7.2-6). 

Fig. 15.2-1 Ribbon diagram showing the structure of the catalytic domain of murine protein kinase A (PKA) in complex with Mg/ATP (lQ24.pdb). The basic architecture that has been observed in all subsequent kinase domain structures is denoted.

Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O Connel J,Cannon RD, McDonald JG, Rodriguez A, Finer-Moore JS, Stroud RM (2014) Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. Proc Natl Acad Sci USAlll 3865-3870... 

The bifunctional terpene cyclases with type I and type II activity are restricted to fungal and plant diterpene cyclases. These enzymes like the monofunctional type I or type II plant enzymes exhibit the apy-domain architecture, but in contrast to the monofunctional terpene cyclases, both the a-domain and the p-domain contain the highly conserved DDXXD and DXDD motifs, respectively, thus establishing the catalytic activities for type I and type II cyclizations within one enzyme. A model system is the recently structurally characterized abietadiene synthase from A. grandis [202] that catalyzes first the class II conversion of... 

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