Cysteine-rich protein

It is now established that cadmium, besides zinc, is accumulated in some native cysteine-rich proteins (e.g., metallothioneins) and the binding mode and sites in the protein are studied and largely understood.57 Also, the detection and study of native Cd-enzymes and Cd-substituted Zn-enzymes is just beginning at the time of writing (for a short survey see ref. 58). 

Kragh KM, Nielsen JE, Nielsen KK, Drebolt S, Mikkelsen JD. Characterization and localization of new antifungal cysteine-rich proteins from Beta vulgaris. Mol Plant-Microbe Interact 1995 8 424—434. 

Metallothionein was first discovered in 1957 as a cadmium-binding cysteine-rich protein (481). Since then the metallothionein proteins (MTs) have become a superfamily characterized as low molecular weight (6-7 kDa) and cysteine rich (20 residues) polypeptides. Mammalian MTs can be divided into three subgroups, MT-I, MT-II, and MT-III (482, 483, 491). The biological functions of MTs include the sequestration and dispersal of metal ions, primarily in zinc and copper homeostasis, and regulation of the biosynthesis and activity of zinc metalloproteins. 

Both copper and zinc appear to be stored in many bacteria in cysteine-rich proteins, called metallothioneins, which will be discussed from a structural point of view later in the chapter. The expression of these metal sequestering, low-molecular weight, cysteine-rich proteins, is often induced by both monovalent Cu(I) and divalent Zn(II), as well as by the non-biologically necessary, but potentially toxic, Ag(I) and Cd(II). 

When animals are fed experimental diets lacking copper or zinc, their copper or zinc status rapidly declines, suggesting that there is not a storage pool of these metals. Thus, while the small, cysteine-rich protein metallothionein (see below) can avidly bind zinc and copper, this may reflect its role in detoxification rather than as a specific storage form. This is reflected by the fact that metallothionein genes are typically expressed at a basal level, but their transcription is strongly induced by heavy metal load. 

To detoxify heavy metals, the liver contains metallothioneins, a group of cysteine-rich proteins with a high af nity for divalent metal ions such as Cd Cu Hg, and Zn T These metal ions also induce the formation of metallothioneins via a special metal-regulating element (MRE) in the gene s promoter (see p. 244). 

Metal ions can serve as effector molecules as well as control the DNA-binding activity of regulatory proteins. An example is the regulation of the metallothionein gene in eucaryotes (Fig. 1.23). The metallothioneins are small, cysteine rich proteins which can specifically bind metal ions like Cu or Zn The complexation of metal ions functions to sequester the ions in a form that is not damaging to the cell. 

Cysteine can be obtained by hydrolysis from cysteine-rich proteins in hair or feathers or from petrochemical sources. Cysteine is an important raw material in Maillard reactions for the preparation of process flavours, but it can also serve as a source of ammonia and hydrogen sulfide for the preparation of flavour chemicals, such as the terpene sulfur compounds mentioned in Sect. 13.2.4 and furfuryl mercaptan mentioned in Sect. 13.4.2.4. 

SCR (S locus cysteine-rich protein) and propose it to be the ligand of SRK [132]. 

S locus cysteine-rich protein self-incompatibility S locus glycoprotein S locus receptor-like kinase systemic wound response protein... 

The addition of copper, zinc, cadmium or mercury to animals results in the synthesis of a cysteine-rich protein called metallothionein.1147-1149 These proteins have been isolated from a number of sources, and have molecular weights in the range 6000 to 12 000 with a cysteine content of about 30-35% of the total amino acid content. They have also been found in microorganisms and plants. These proteins are thought to play an important role in the storage of zinc and copper, and as a result of their storage capacity, are able to bind and detoxify cadmium and mercury. 

Pseudomonas putida growing on 3 mM cadmium synthesizes three cysteine-rich proteins of molecular weight 4000 to 7000, containing four to seven cadmium, zinc and copper atoms per molecule. The use of I13Cd NMR on the major cadmium protein shows it to be related to cadmium metallothionein, but with some significant differences.I223b... 

The Bowman-Birk type protease inhibitors represent a class of low molecular weight, cysteine-rich proteins found in legume seeds (.10). The major Bowman-Birk inhibitor in soybean seeds is a double-headed protein capable of blocking the activity of both trypsin and chymotrypsin. This protein represents approximately 4% of the total protein in soybean seeds (1J ). In contrast to the soybean trypsin inhibitor (Kunitz), the "double-headed inhibitor (referred to as BB) is typical of protease inhibitors present in a large number of legume seeds for example, peanuts (12) chick peas (33)5 kidney beans (3JO adzuki beans (33) lima beans (16). 

Several plant proteins have been isolated that inhibit the metalloprotease carboxypeptidase A [205-217] (Table 7), notably potato carboxypeptidase inhibitor PCI [207-217] (Table 7). PCI is a small, cysteine-rich protein with a compact knotted structure determined by 3 disulphide links. The C-terminal region inserts into the active site of the carboxypeptidase. The C-terminal glycine is cleaved and remains trapped in the active site, this representing an example of suicide inactivation [207-216]. 

The squash family (Cucurbitaceae) family of serine PIPs are very small circa 3 kDa), cysteine-rich proteins (6 cysteines being involved in 3 disulphide linkages) [537-561]. These small proteins have extraordinary affinities for the target serine proteases (K values in the nanomolar and picomolar range) (Table 17). The serine proteases variously inhibited by squash family PIPs include elastase, trypsin, kallikrein and blood clotting protease factors Xa, XIa and Xlla (Table 17). Of particular note are the squash family PIPs MCoTI-I and MCoTI-U from Momordica cochinensis... 

FIGURE 22.1 Pentameric structure of IgM IgM is composed of a pentamer of the basic four chain structure held together by inter H chain disulfide bonds. The heavy chain (p) has four constant domains. A small, cysteine rich protein called J chain initiates cross linking of C3 and C4 of five IgM monomers to make the circulating, pentameric form of IgM. 

Coxl7, an 8.1-kDa cysteine-rich protein, was the first copper chaperone to be identified. Saccharomyces cerevisiae harboring mutations in coxl 7 are respiratory deficient, a phenotype resulting from their inability to assemble a functional cytochrome c oxidase complex (Glerum et al., 1996a). coxl7 mutant yeast are, however, able to express all the subunits of the cytochrome c oxidase complex, indicating that the lesion must lie in a posttranslational step that is essential for assembly of the functional complex in the mitochondrial membrane. Unlike other cytochrome c... 

Metallothioneins are cysteine-rich proteins capable of binding a range of metal ions, such as Zn, Cu, Cd, and Hg, via thiolate coordination. The structure of a Zn/Cd metallothionein shows a triangular array of metals, each coordinated tetrahedrally to thiolate cysteines. 

COX 17 is a small cysteine rich protein that can bind copper in the form of a binuclear cuprous-thiolate cluster. The COX 17 protein has been localized to both the cytoplasm and mitochondria, and because of this dual location, COX 17 was proposed to shuttle copper ions between these two compartments. However, work by D. Winge has shown that only the mitochondrial form of COX 17 is needed for copper activation of cytochrome oxidase. The role of the cytoplasmic form is not understood. In any case, mitochondrial COX 17 is believed to capture IMS copper and then transfer the metal to a second set of accessory proteins for the Cua site of cytochrome oxidase SCOl and SC02. 

Peptides and proteins could be efficient metal binding ligands, because they have the functional groups for metal binding in their amino acid residues, and they can be produced at low cost by recombinant technologies. While many peptides and proteins are known to work as metal transport proteins in biological systems, metallothioneins (cysteine rich proteins with molecular weight of ca. 7 kDa) have attracted researchers attention for decades because they bind heavy metals in vivo [2]. The metallothioneins are considered to be involved in detoxication and metabolism of heavy metals. 

Muramatsu Y,TsujleM, KohdaY, Pham B, PerantonI AO, Zhao FI, Jo SK,Yuen PS, Craig L, Flu X, Star RA Early detection of cysteine rich protein 61 (CYR61,CCN1) In urine following renal Ischemic reperfuslon Injury. Kidney Int. 62 1601-1610,2002... 

Metallothionein, metal-binding proteins and phytochelatins (see Gagne and Blaise, Chapter 7 of this volume). Metallothioneins are low molecular weight, cysteine-rich proteins with a high affinity for transition metals. After they were first discovered in the kidney cortex of the horse they have been detected in a variety of animal species. It is widely accepted that metallothioneins are multifunctional proteins primarily involved in the homeostasis of essential trace metals, zinc-mediated gene regulation, and in the protection of cells against oxidative... 

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