Proteins triose phosphate isomerase

Figure 1.29 Alternative cartoon depictions of proteins, (a) surface display structure of small metal rich protein cytochrome c (horse heart) (pdb Ihrc) showing Van der Waal s surface coloured for positive charge (blue) and for negative charge (red). Ball and stick representations of iron-porphyrin macrocycle (prosthetic group) are shown (red) for each subunit with central iron ion rendered as Van der Waals sphere (light blue) (b) CPK structure of cytochrome c in which all polypeptide atoms are rendered as Van der Waals spheres (purple). Porphryin and iron ion are shown as in Fig. 1.28 (c) schematic display structure (top view) of parallel a/p-protein triose phosphate isomerase (chicken muscle) (pdb Itim) with a-helix shown as cylinders (red), 8-strands as arrowed ribbons (light blue), loop structures (random coil) as rods (light grey) (d) schematic display structure (side view) of triose phosphate isomerase, otherwise as for (c).

FIGURE 6.28 Examples of protein domains with different numbers of layers of backbone strnctnre. (a) Cytochrome c with two layers of a-helix. (b) Domain 2 of phosphoglycerate kinase, composed of a /3-sheet layer between two layers of helix, three layers overall, (c) An nnnsnal five-layer strnctnre, domain 2 of glycogen phosphorylase, a /S-sheet layer sandwiched between four layers of a-helix. (d) The concentric layers of /S-sheet (inside) and a-helix (outside) in triose phosphate isomerase. Hydrophobic residnes are bnried between these concentric layers in the same manner as in the planar layers of the other proteins. The hydrophobic layers are shaded yellow. (Jane Richarelson)... 

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.)...

N6. Neubauer, B. A., Pekrun, A., Eber, S. W Lakomek, M and Schroter, W., Relation between genetic defect, altered protein structure, and enzyme function in triose-phosphate isomerase (TPI) deficiency. Eur. J. Pediatr. 151,232a (1992). 

Petsko, G. A., Phillips, D. C., Williams, R. J. P. and Wilson, I. A. (1978). On the protein crystal chemistry of chloroplatinite ions general principles and interactions with triose phosphate isomerase. /. Mol. Biol. 120, 345-359. 

The eight-stranded P cylinder of plastocyanin (Fig. 2-16A) is somewhat flattened and can also be regarded as a P sandwich.116118 However, the P barrel of triose phosphate isomerase (see Fig. 2-28) is surrounded by eight a helices which provide additional stability and a high symmetry. Bacterial outer membranes contain pores created by very large P cylinders within proteins called porins.119120 Tire one shown in Fig. 8-20 has 16 strands. 

A 28 kDa protein was identified as the target of a mAb that conferred partial protection (41-49%) on mice (Harn etal., 1992). Peptide sequencing of the protein revealed it as the 5. mansoni homologue of mammalian triose phosphate isomerase (TPI), present in all stages of the parasite and transiently on the surface... 

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... 

There are numerous cases of proteins for which structures have been determined in more than one state of ligation. In some cases, the structures undergo little change, except perhaps for specific and localized changes associated with particular functional residues—for example, triose phosphate isomerase. Other cases, such as... 

Keeling PJ, Doolittle WF (1997) Evidence that eukaryotic triose-phosphate isomerase is of a-proteobacterial origin. Proc Natl Acad Sci USA 94 1270-1275 Kollman JM, Doolittle RF (2000) Determining the relative rates of change for prokaryotic and eukaryotic proteins with anciently duplicated paralogs. J Mol Evol 51 173-181 Kumar S, Rzhetsky A (1996) Evolutionary relationships of eukaryotic kingdoms. J Mol Evol 42 183-193... 

FIGURE 12.36. Various types of protein tertiary structure, (a) An antiparallel a structure (cytochrome 6502) an up-and-down helix bundle (Ref. 113), (b) an antiparallel / structure (Cu,Zn superoxide dismutase) a Greek key (3 barrel (Ref. 114), and (c) and a parallel aj structure (triose phosphate isomerase) a singly wound parallel 0 barrel (Ref. 115). (Courtesy Jane S. Richardson)... 

P barrel The folding of a polypeptide chain to form a barrel-shaped structure with eight p strands as the lining. Eight a helices lie outside this p sheet. Both the a helices and the P strands follow a right-handed spiral around the axis of the barrel. The amino acid sequence in such a protein is such that p sheet and a helix alternate to give Pa)s- This motif was first seen in triose phosphate isomerase, and has since been observed in many other protein structures. 

A fusion of the signal sequence of the periplasmic protein p-lactamase with chicken triose-phosphate isomerase (a cytoplasmic enzyme) also remains uncleaved and in the cytoplasm (Kadonaga et al.,... 

A number of other enzymopathic substances (e.g., pyruvate kinase. Chapter 13 and pyrimidine-5 -nucleotidase. Chapter 27), abnormal hemoglobins (Chapter 28), and abnormalities of the erythrocyte cytoskeleton (Chapter 10) may cause hemolytic anemia. Because many enzymes in the red cell are identical to those in other tissues, defects in these enzymes may have pleiotropic effects. Thus, in addition to hemolytic anemia, triose phosphate isomerase deficiency causes severe neuromuscular disease, and phospho-fructokinase deficiency causes a muscle glycogen storage disease (Chapter 13). Mutations that result in decreased enzyme stability are usually most strongly expressed in erythrocytes because of their inability to synthesize proteins. 

BLA.ST away. Using the National Center for Biotechnology Information Web site (www.ncbi.nlm.nih.gov), find the se quence of the enzyme triose phosphate isomerase from E, coli. Use this sequence as the query for a protein—protein BLAST search. In the output, find the alignment with the sequence of triose phosphate isomerase from human beings Homo sapiens]. How many identities are observed in the alignment ... 

The classical polypeptide conformations are the a-helix and the parallel and antiparallel -pleated sheets due to Pauling and colleagues [46,47]. These conformations can occur separately in fibrous proteins or they can often be beautifully combined, as in certain globular proteins such as triose phosphate isomerase [48] and carboxypeptidase A [49]. The interesting motifs constituting the anatomy of some globular proteins have been emphasized by the work of Richardson [50], and a combination of pleated sheet and a-helix was early proposed as a structural motif for dynamic voltage dependent channel formation [51,52]. Our concern here, however, is to characterize separately these conformations in order that a view of more complex combinations of these structures can be correctly obtained. 

Figure 1. Some protein structures solved by X-ray crystallography. The figure illustrates the different secondary structure assemblies. a-Helices are represented by spirals or cylinders -strands by arrows, (a) Hemerythrin, an all a-protein. (b) Superoxide dismutase, an all /7-protein, (c) Lysozyme, an a -i- /7 protein, (d) and (e) Two orthogonal views of the NAD binding domain of lactate dehydrogenase, an a/p protein, (f) Triose phosphate isomerase, an a/p structure, (g) A DNA binding protein, the CAP protein from E. coli. (h) Influenza virus haemaglutinin. (i) Influenza virus neuraminidase. From Blake and Johnson [12b], which also contains references to the original sources of these structures.

In some cases, families are further grouped into clans. The largest such clan is the glycosyl hydrolase Clan A (clan GH-A), all of which have a protein fold of eight alternating a-helices and p-sheets, giving the (p/a)g sructure, sometimes called a TIM barrel because it was first encountered with triose phosphate isomerase. 

The enediolate is stabilised to phosphate loss by the protein of triose phosphate isomerase, but occasionally comes off the enzyme and yields methylglyoxal, which is detoxified by another hydroxy ketone isomerase, glyoxylase. 

Figure 1. Schematic representations of protein structures (a) myohemerythrin, an a-helical protein with antiparallel helices ( >) V2 domain of an immunoglobulin, a (3-sheet protein (c) triose phosphate isomerase, a parallel a-ff protein with a central (3 barrel (d) carboxypepti-dase, a parallel a- 3 protein with a central ( -sheet structure (e)para-hydroxybenzoate hydrolase, a complex protein structure with more than one domain. (From Ref. S3 courtesy of J. Richardson.)...

Table 1 summarizes the general characteristics of representative urease, hydrogenase and CODHs. As it will be further discussed below, the X-ray structures of only two Ni-containing proteins, urease and hydrogenase, are known [16, 17]. The former has the well known triose phosphate isomerase (TIM) barrel topology (Fig. 1) whereas the latter displays a so far unique folding (Fig. 2). The next challenge will be the elucidation of the crystal structures of the CODH/ACS enzyme of Clostridium thermoaceticum and of the simpler CODH from Rhodospirillum rubrum. 

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