Domain catalytic

Figure 4.15 Schematic diagram of the enzyme tyrosyl-tRNA synthetase, which couples tyrosine to its cognate transfer RNA. The central region of the catalytic domain (red and green) is an open twisted a/p stmcture with five parallel p strands. The active site is formed by the loops from the carboxy ends of P strands 2 and S. These two adjacent strands are connected to a helices on opposite sides of the P sheet.

Ras proteins and the catalytic domain ofGa have similar three-dimensional structures... 

Figure 13.6 Schematic diagram of Go. from transducin with a bound GTP analog. The polypeptide chain is organized Into two domains a catalytic domain (light red) with a structure similar to Ras, and a helical domain (green) which is an Insert in the loop between al and P2. There are three switch regions (violet) that have different conformations in the different catalytic states of Go.. The GTP analog (brown) Is bound to the catalytic domain in a cleft between the two domains. (Adapted from J. Noel et al.. Nature 366 654-663, 1993.)...

Figure 13.15 Schematic diagram of the heterotrimeric Gap complex based on the crystal structure of the transducin molecule. The a suhunit is hlue with some of the a helices and (5 strands outlined. The switch regions of the catalytic domain of Gq are violet. The (5 suhunit is light red and the seven WD repeats are represented as seven orange propeller blades. The 7 subunit is yellow. The switch regions of Gq interact with the p subunit, thereby locking them into an inactive conformation that binds GDP but not GTP.

Tesmer, J.J.G., et al. Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsa.GTPyS. Science 278 1907-1916, 1997. 

All PLC isozymes have conserved catalytic domains designated X and Y, and a C2 domain similar to that in cPLA2 (Fig. 2). In addition, the (3, y and 8 isozymes have pleckstrin homology (PH) domains and EF-hand domains located in theN-teiminal region. The y isozymes differ in that they have Src homology domains (SH2 and SH3) and an additional PH domain split by the SH domains. The (3 and y isozymes are of140-155 kDa mass, whereas the 8 isozymes are smaller (85 kDa) and the o isozyme is larger (240 kDa). 

Grodsky N, Li Y, Bouzida D et al (2006) Structure of the catalytic domain of human protein kinase C (311 complexed with a bisindolylmaleimide inhibitor. Biochemistry 45 13970-13981... 

Besides cytoplasmic protein kinases, membrane receptors can exert protein kinase activity. These so-called receptor tyrosine kinases (RTK) contain a ligandbinding extracellular domain, a transmembrane motif, and an intracellular catalytic domain with specificity for tyrosine residues. Upon ligand binding and subsequent receptor oligomerization, the tyrosine residues of the intracellular domain become phosphory-lated by the intrinsic tyrosine kinase activity of the receptor [3, 4]. The phosphotyrosine residues ftmction as docking sites for other proteins that will transmit the signal received by the RTK. 

Genome sequencing revealed approximately 100 human PTP genes [2], compared with 90 human protein tyrosine kinase genes, suggesting similar levels of complexity among the opponents. The catalytic domain... 

The current understanding on activation of Tec kinases fits into a two-step model. In the first step an intramolecular interaction between the SH3 domain and aproline-rich region in the TH domain is disrupted by binding ofthe PH domain to phosphoinositides, G protein subunits, or the FERM domain of Fak. These interactions lead to conformational changes of Tec and translocation to the cytoplasmic membrane where, in a second step, Src kinases phosphorylate a conserved tyrosine residue in the catalytic domain thereby increasing Tec kinase activity. Autophosphorylation of a tyrosine residue in the SH3 domain further prevents the inhibitory intramolecular interaction resulting in a robust Tec kinase activation. 

Rieske proteins are constituents of the be complexes that are hydro-quinone-oxidizing multisubunit membrane proteins. All be complexes, that is, bci complexes in mitochondria and bacteria, b f complexes in chloroplasts, and corresponding complexes in menaquinone-oxidizing bacteria, contain three subunits cytochrome b (cytochrome 6e in b f complexes), cytochrome Ci (cytochrome f in b(,f complexes), and the Rieske iron sulfur protein. Cytochrome 6 is a membrane protein, whereas the Rieske protein, cytochrome Ci, and cytochrome f consist of water-soluble catalytic domains that are bound to cytochrome b through a membrane anchor. In Rieske proteins, the membrane anchor can be identified as an N-terminal hydrophobic sequence (13). 

The bacterial Rieske proteins contain 3—20 extra residues in the catalytic domain these insertions occur in the helix—loop structure and in the loop /35-/S6 (see Section III,B). The insertion of a single residue is observed in some bacterial sequences between the flexible linker and f3 strand 1 as well as in the Pro loop. Twenty-eight residues are fully conserved between 11 mitochondrial and 6 bacterial sequences 22 of these conserved residues are located in the cluster binding subdomain. 

In NDO, the corresponding loop is much longer and does not interact with the environment of the Rieske cluster, hut is involved in subunit interactions with the catalytic domain in a neighboring subunit (11). 

The cluster is coordinated at the tip of the cluster binding subdomain. Fe" (Fe-2) is close to the surface of the protein with its histidine ligands fully exposed to the solvent, whereas Fe " (Fe-1) is buried within the protein and surrounded by the three loops forming the cluster binding subdomain. However, in NDO the histidine ligands are not solvent accessible, but buried at the interface between the Rieske domain and the catalytic domain both histidine ligands form hydrogen bonds with acidic side chains in the catalytic site close to the catalytic iron. 

In be complexes bci complexes of mitochondria and bacteria and b f complexes of chloroplasts), the catalytic domain of the Rieske protein corresponding to the isolated water-soluble fragments that have been crystallized is anchored to the rest of the complex (in particular, cytochrome b) by a long (37 residues in bovine heart bci complex) transmembrane helix acting as a membrane anchor (41, 42). The great length of the transmembrane helix is due to the fact that the helix stretches across the bci complex dimer and that the catalytic domain of the Rieske protein is swapped between the monomers, that is, the transmembrane helix interacts with one monomer and the catalytic domain with the other monomer. The connection between the membrane anchor and the catalytic domain is formed by a 12-residue flexible linker that allows for movement of the catalytic domain during the turnover of the enzyme (Fig. 8a see Section VII). Three different positional states of the catalytic domain of the Rieske protein have been observed in different crystal forms (Fig. 8b) (41, 42) ... 

Fig. 8. (a) Structure of the full-length Rieske protein from bovine heart mitochondrial bci complex. The catalytic domain is connected to the transmembrane helix by a flexible linker, (b) Superposition of the three positional states of the catalytic domain of the Rieske protein observed in different crystal forms. The ci state is shown in white, the intermediate state in gray, and the b state in black. Cytochrome b consists of eight transmembrane helices and contains two heme centers, heme and Sh-Cytochrome c i has a water-soluble catalytic domain containing heme c i and is anchored by a C-terminal transmembrane helix. The heme groups are shown as wireframes, the iron atoms as well as the Rieske cluster in the three states as space-filling representations. 

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