Enzyme domain function

Small GTPases of the Rho family are ADP-ribosylated (e.g., at Asn4l of RhoA) and inactivated by C3-like toxins from Clostridium botulinum, Clostridium limosum, and Staphylococcus aureus. These proteins have a molecular mass of 23-30 kDa and consist only of the enzyme domain. Specific inhibition of Rho functions (Rho but not Rac or Cdc42 are targets) is the reason why C3 is widely used as a pharmacological tool [2]. 

Important members of this toxin family are Clostridium difficile toxins A and B, which are implicated in antibiotics-associated diarrhea and pseudomembranous colitis. The large clostridial cytotoxins are single-chain toxins with molecular masses of 250-308 kDa. The enzyme domain is located at the N terminus. The toxins are taken up from an acidic endosomal compartment. They glucosylate RhoA at Thr37 also, Rac and Cdc42 are substrates. Other members of this toxin family such as Clostridium sordellii lethal toxin possess a different substrate specificity and modify Rac but not Rho. In addition, Ras subfamily proteins (e.g., Ras, Ral, and Rap) are modified. As for C3, they are widely used as tools to study Rho functions [2] [4]. 

This class of receptors transmits signals carried by hormones and growth factors. The structure consists of an extracellular domain for binding ligands and a cytoplasmic enzyme domain. The function of kinases is to enable phosphorylation. Phosphorylation regulates most aspects of cell life. 

Additional Enzyme Domains that Function in the NRPS Assembly Line... 

Figure 12.18. Output of Pfam search results. Pfam search is performed with amino acid sequence derived from lipoamide dehydrogenase (Schizosaccharomyces pombe). The table for the trusted matches from Pfam-A for pyr redox (pyridine nucleotide disulfide oxidoreductase) and pyr redox dim (pyridine nucleotide disulfide oxidoreductase, dimerization) domains and their alignments (partial) to HMMs ( ->) are shown. The trusted matches from Pfam-B, the potential matches (Thi4 for thiamine biosynthetic enzyme domain), and the bead-on-a-string sketches are not shown. Select the linked domain name to view the functional description of the domain. The HMM alignments are followed by an option button (Align to seed or Align to family) that enables the user to view/save the multiple alignment of each matched family.

Cirilli et al.11171 cloned the gene of diaminopimelate epimerase from Haemophilus influenzae, and purified and crystallized the enzyme. The enzyme is monomeric and has a unique protein fold, in which the amino terminal and carboxyl terminal halves of the molecule fold into structurally homologous and superimposable domains (Fig. 17-13). Cys 73 of the amino terminal domain is found in the disulfide linkage, at the domain interface, with Cys 217 of the carboxy terminal domain 117. Thus, it is most conceivable that these two cysteine residues stay in reduced form in the active enzyme and function as the acid and base in the mechanism. Koo and Blanchard 118 explored a number of kinetic and isotope approaches to clarify the mechanism of the enzyme. However, which of the two cysteine residues is responsible for proton abstraction from the two enantiomeric Ca-H bonds is not yet known. 

Domain 1 contains the first 8 -strands as well as a binding site for a sodium ion and for D-galactose. It is yet unknown whether the sodium ion is of importance for the enzyme s function. Domain 1 is of some distance from the copper center and its function is not clearly defined. It is possibly a chaperone for the correct folding of the enzyme, in which domain 1 is utilized as a blueprint for the complicated folding of domain 2. The D-galactose binding site of domain 1 may possibly be needed to attach the enzyme to the cell walls of trees, the natural habitat of Dactylium dendroides [30]. 

A bacterial flavohemoglobin, which contains a globin domain fused to a flavin/NADH binding domain, functions enzymatically as a nitric oxide dioxygenase, using a catalytic cycle similar to that in Figure 10. The role of this enzyme is apparently to detoxify nitric oxide produced by the body in response to bacterial infection. The distal pocket of flavohemoglobins more closely... 

Part of a protein sequence can function independently of the rest of the protein. For example, a protein may contain a DNA binding domain and an enzyme domain. 

I palymeiase domain EH 3 exonadease domain n other domains, functional motifs and regions of unknown function H regions of homology with the yeast (Sc) enzyme EH BRCT domain EH DNA binding/dRP ly ase domain seiine-proline domain I helicase-like domain... 

A., Atomi, H., and Nidetzky, B. (2009) Short-chain a-l,4-glucan phospho-rylase having a truncated N-terminal domain functional expression and characterization of the enzyme from Sulfolobus solfataricus. Biochim. Bio-phys. Acta, 1794, 1709-1714. 

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