Two-domain structure

Figure 5-6. Examples of tertiary structure of proteins. Top The enzyme triose phosphate isomerase. Note the elegant and symmetrical arrangement of alternating p sheets and a helices. (Courtesy of J Richardson.) Bottom Two-domain structure of the subunit of a homodimeric enzyme, a bacterial class II HMG-CoA reductase. As indicated by the numbered residues, the single polypeptide begins in the large domain, enters the small domain, and ends in the large domain. (Courtesy ofC Lawrence, V Rod well, and C Stauffacher, Purdue University.)...

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the NAD(P)H-dependent reduction of 5,10-methylenetetrahydrofolate (CH2-THF) to 5-methyltetrahydrofolate (CH3-THF). CH3-THF then serves as a methyl donor for the synthesis of methionine. The MTHFR proteins and genes from mammalian liver and E. coli have been characterized,12"15 and MTHFR genes have been identified in S. cerevisiae16 and other organisms. The MTHFR of E. coli (MetF) is a homotetramer of 33-kDa subunits that prefers NADH as reductant,12 whereas mammalian MTHFRs are homodimers of 77-kDa subunits that prefer NADPH and are allosterically inhibited by AdoMet.13,14 Mammalian MTHFRs have a two-domain structure the amino-terminal domain shows 30% sequence identity to E. coli MetF, and is catalytic the carboxyterminal domain has been implicated in AdoMet-mediated inhibition of enzyme activity.13,14... 

Stem-Bach, Y., Bettler, B., Hartley, M., Sheppard, P. O., O Hara, P. J., and Heinemann, S. F. (1994) Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins. Neuron 13,1345-1357. 

X-ray diffractional analysis of crystalline human IL-5 reveals a two-domain structure, with each domain consisting of four a-helical stretches and one )S-stretch consisting of two antiparallel jS-strands. 

Stahlberg, J., Johansson, G, and Pettersson, G. 1991. A new model for enzymatic hydrolysis of cellulose based on the two-domain structure of cellobiohydrolase I. Bio/Technology 9, 286-290... 

Cytochrome c, is an amphiphilic protein with a molecular weight of 28-31000. Weiss et al. [212] found that it may be isolated only with the help of a detergent. However, by mild proteolysis they could release the haem-binding domain from the rest of the protein. This segment is soluble in aqueous solutions. The amino acid sequence of the bovine protein [181] shows that it has only one continuous hydrophobic segment that is close to the C-terminus. This segment probably acts as an anchor to the membrane. The covalently bound haem is located in the water-soluble part, with its plane perpendicular to the membrane plane [206], The two-domain structure makes the architecture of cytochrome c, very similar to that of microsomal cytochrome [213]. 

The salivary proline-rich proteins have a two-domain structure, a proline poorN-terminal domain that is acidic or basic and determines enamel binding, and a proline-rich C-terminal domain that determines bacterial binding. Individual variations in acidic proline-rich proline allelic composition and in the amount of salivary agglutinin, a secreted innate immunity protein that binds bacteria, may account for differences in biofilm composition and dental caries susceptibility. 

Fig. 7. Transition from a two-domain structure to a three-domain structure in an ABC triblock copolymer lamellar phase. Although state ii is thermodynamically the most stable state, transition to this state from i is hindered because of the high free energy cost in switching the orientation of the bridges and in turning the loops into bridges. Thus, a kinetically more likely process is for the A and C blocks from the bridge conformation to separate laterally, with the loops straddling the interfaces between the A and the C domains.

The two-domain, structural motif in FNR represents a common structural feature in a large class of enzymes that catalyze electron transfer between a nicotinamide dinucleotide molecule and a one-electron carrier. Beside the photosynthetic electron-transfer enzyme, others non-photosynthetic ones include flavodoxin reductase, sulfite reductase, nitrate reductase, cytochrome reductase, and NADPH-cyto-chrome P450 reductase. FNR belongs to the group of so-called dehydrogenases-electron transferases, i.e., flavoproteins that catalyze electron transfer from two, one-electron donor molecules to a single two-electron acceptor molecule. 

Fig. 2. Ribbon diagram of SEB structure as representative of SEs and related toxins. The diagram has been constructed using Cn3D version 4.1 program. SEs andTSST-1 have a two-domain structure, with a solvent-accessible a-helix in the center. The MHC class II and TCR recognition sites are marked [30]. 

In the C-terminal domain are five helices in a closed bundle. This characteristic fold is typical of thermolysin-like peptidases. Clan MC contains metallocarbox-ypeptidases which belong to only one family (M14) which is divided into the subfamilies A, B and C. Typical for this clan is that one zinc ion is tetrahedrally coordinated by a water molecule, two histidine and one glutamate residues. Clan MF includes aminopeptidases that require cocatalytic zinc ions for their enzymatic activity. The well-known leucyl aminopeptidase has a two-domain structure bearing the active site in the C-terminal domain. Whereas exopeptidases of clan MG require cocatalytic ions of cobalt or manganese, clan MH contains the third group of metallopeptidases that also require cocatalytic metal ions, but here these are all zinc ions. The third clan in which cocatalytic metal ions are necessary is clan MF with zinc or manganese. Only one catalytic zinc ion is required for peptidases of clans MA, MB, MC, MD and ME. 

In many cell types, a rise in the cAMP level may produce a response that is required in one part of the cell but Is unwanted, perhaps deleterious, in another part. A family of anchoring proteins localizes PKA Isoforms to specific subcellular locations, thereby restricting cAMP-dependent responses to these locations. These proteins, referred to as A kinase associated proteins (AKAPs), have a two domain structure with one domain conferring a specific subcellular location and another that binds to the regulatoiy subunit of protein kinase A. 

The conformations of apo A1 and apo E molecules in spherical lipoprotein particles are governed by the size and lipid composition of the particle. Thus, the two-domain structure of apo E has been shown to lead to two different lipid-bound conformations on... 

The diversity of all these reactions can be explained by the three-dimensional organization of the GST into a two-domain structure. The first domain contains the conserved active site responsible for catalysis, whereas the variable second domain, which interacts with the xenobiotic substrate of the reaction, provides substrate specificity and versatility. 

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