Protein 3 barrel

Godzik A, J Skolnick and A Kolinski 1992. Simulations of the Folding Pathway of Triose Phosj Lsomerase-type a// Barrel Proteins. Proceedings of the National Academy of Sciences USA 89 1 2633. 

Lesk, A.M., Branden, C.-L, Chothia, C. Structural principles of a/p barrel proteins the packing of the interior of the sheet. Proteins 5 139-148, 1989. 

Amaro, R. Luthey-Schulten, Z., Molecular dynamics simulations of substrate channeling through an alpha-beta barrel protein, Chem. Phys. 2004, 307, 147-155... 

Buchanan, S. K. (1999). Beta-barrel proteins from bacterial outer membranes structure, function and refolding, Curr. Opin. Struct. Biol., 9, 455-461. 

Initially, it was suspected that the nitrophorins were insect hemoglobins. Indeed, they showed 45-48% homology with monomeric hemoglobins from insects, annelids, mollusks, nematodes, and even human 3 chains and leghemoglobin (44). However, in due time it became clear that these proteins were not globins at all, but rather, beta-barrel proteins called lipocalins (see Section III). As for the four nitrophorins, the sequences of NPl and NP4 are 90% identical, whereas those of NP2 and NP3 are 79% identical NPl and NP2, however, are only 38% identical. 

The insertion and assembly of -barrel outer membrane proteins, including Tom40, are assisted by the sorting and assembly machinery (SAM) complex (Fig. 1). The SAM complex consists of four subunits, the core translocase Sam50, which is itself a putative -barrel protein (Kozjak et al. 2003 Paschen et al. 2003 Gentle et al. 2004), and the additional proteins Sam35,... 

The insertion of (i-barrel precursors is one of the two translocation processes, besides the sorting of inner membrane and IMS proteins, that are clearly derived from a eubacterial translocation system. (1-Barrel proteins are exclusively found in the outer membranes of Gram-negative bacteria and of endosymbiotic organelles such as mitochondria and plastids (Wim-... 

Ishikawa D, Yamamoto H, Tamura Y, Moritoh K, Endo T (2004) Two novel proteins in the mitochondrial outer membrane mediate beta-barrel protein assembly. J Cell Biol 166 621-627... 

Fig. 2c. It can be seen that at 530 nm, the fluorescence decays mono-exponentially with the fluorescence lifetime of 3.24 ns. The rise of the emission seen below 50 ps in the corresponding FlUp data is obviously not resolved here. In contrast, the TCSP data at 450 nm is described by a triple-exponential decay whose dominant component has a correlation time well below the time resolution. This component is obviously equivalent to the fluorescence decay observed in the FlUp experiment. A minor contribution has a correlation time of about 3.2 ns and reflects again the fluorescence lifetime that was also detected at 530 nm. The most characteristic component at 450 nm however has a time constant of about 300 ps. It is important to emphasize that this 300 ps decay does not have a rising counterpart when emission near the maximum of the stationary fluorescence spectrum is recorded. In other words, the above mentioned mirror image correspondence of the fluorescence dynamics between 450 nm and 530 nm holds only on time scales shorter than 20 ps. Finally, in contrast to picosecond time scales, the anisotropy deduced from the TCSPC data displays a pronounced decay. This decay is reminiscent of the rotational diffusion of the entire protein indicating that the optical chromophore is rigidly embedded in the core of the 6-barrel protein.

The degradation of mandelic acid by the bacterium Pseudomonas putida (Chapter 25) is initiated by mandalate racemase, another (a/(3)8-barrel protein.101 X-ray structures of bound inhibitors together with modeling suggest that the side chain of Lys 264 is the catalytic base that abstracts the a-H from S-mandelate (Fig. 13-5) and that the catalytic pair of His 297 and Asp 270 acts as proton donor, or, in the reverse direction, as catalytic... 

Treatment with sodium borohydride of the enzyme-substrate complex of aldolase A and dihydroxyacetone phosphate leads to formation of a covalent linkage between the protein and substrate. This and other evidence suggested a Schiff base intermediate (Eq. 13-36). When 14C-containing substrate was used, the borohydride reduction (Eq. 3-34) labeled a lysine side chain in the active site. The radioactive label was followed through the sequence determination and was found on Lys 229 in the chain of 363 amino acids.186/188 188b Tire enzyme is another (a / P)8-barrel protein and the side chain of Lys 229 projects into the interior of the barrel which opens at the C-terminal ends of the strands. The conjugate base form of another lysine,... 

Cold-shock /3-barrel proteins, folding kinetics 551... 

Active-site architecture retained In this case, the active site is able to support alternative reactions with shared functional groups in a different mechanistic or metabolic context.The study of a/jS-barrel proteins, also termed ()3a)8-barrel... 

The earliest currently discernible ancestor in the histidine biosynthesis pathway was a (j8a)4-half-barrel protein which gene-duplicated into two initially identical half-barrels which fused to form an ancestral a/j8-barrel protein. The second gene duplication step led to diversification into two enzymes with distinct catalytic activities. 

As already discussed in Chapter 11, there are more than 10 000 protein structures known but only about 30 3D structure types. This might be traced to a limited number of possible stable polypeptide structures but most probably reflects the evolutionary history of the diversity of proteins. There are structural motifs which repeat themselves in a multitude of enzymes which are otherwise neither structurally nor functionally related, such as TIM barrel proteins, four-helix bundle proteins, Rossmann folds, or a/j3-folds of hydrolases (Figure 16.1). 

In proteins with a symmetric structure, circular permutation can account for the shift of active-site residues over the course of evolution. A very good model of symmetric proteins are the (/Ja)8-barrel enzymes with their typical eightfold symmetry. Circular permutation is characterized by fusion of the N and C termini in a protein ancestor followed by cleavage of the backbone at an equivalent locus around the circular structure. Both fructose-bisphosphate aldolase class I and transaldolase belong to the aldolase superfamily of (a/J)8-symmetric barrel proteins both feature a catalytic lysine residue required to form the Schiff base intermediate with the substrate in the first step of the reaction (Chapter 9, Section 9.6.2). In most family members, the catalytic lysine residue is located on strand 6 of the barrel, but in transaldolase it is not only located on strand 4 but optimal sequence and structure alignment with aldolase class I necessitates rotation of the structure and thus circular permutation of the jS-barrel strands (Jia, 1996). 

The study of //J-barrel proteins, also called TIM barrels after the first enzyme investigated in this class, triose phosphate isomerase, or (/3a)8-barrel enzymes after the... 

Figure 16.10 Separation of catalysis N and stability domains in barrel proteins...

MR, an a/f-barrel protein, features a high degree of similarity with muconate-lactonizing enzyme (MLE) of the /3-ketoadipate metabolism 26% sequence identity, the same symmetry and organization of subunits (octamer), a divalent metal ion requirement (Mn2+ for MLE, Mg + for MR). As MLE is almost ubiquitous among Pseudomonas, compared to 5% frequency of MR, it can be concluded that MLE is the older enzyme and probably the precedessor of MR. 

As all enzymes of the mandelate path are located on one operon, the other four enzymes could also be identified, cloned, and sequenced. (S)-Mandelate dehydrogenase [(S)-ManDH] features similarities to glycolate oxidase and flavocyto-chrome b2 (a lactate-DH) both are a/f-barrel proteins and require FMN as cofactor as does (S)-ManDH. It is reasonable to conclude that in this case nature has also sequestered a template that already catalyzes a chemistry similar to the desired reaction. 

---