Proteins important examples

The side chains of the 20 different amino acids listed in Panel 1.1 (pp. 6-7) have very different chemical properties and are utilized for a wide variety of biological functions. However, their chemical versatility is not unlimited, and for some functions metal atoms are more suitable and more efficient. Electron-transfer reactions are an important example. Fortunately the side chains of histidine, cysteine, aspartic acid, and glutamic acid are excellent metal ligands, and a fairly large number of proteins have recruited metal atoms as intrinsic parts of their structures among the frequently used metals are iron, zinc, magnesium, and calcium. Several metallo proteins are discussed in detail in later chapters and it suffices here to mention briefly a few examples of iron and zinc proteins. 

Stimulation and inhibition of the enzyme by the GPCR-G-protein cycle occur by analogous mechanisms. Agonists induce hormone receptors to increase a Ga-GDP-GTP exchange and subsequent Ga 3y dissociation (GDP-a py + GTP GTP-ax + [3y + GDP) (Fig. 4). Consequently, agents that affect either the dissociation of either G or Gs, or the association of their respective as, a , or (3y subunits with adenylyl cyclase could affect rates of cAMP formation in enzyme preparations or in intact cells and tissues. There are several important examples. Gas is stably activated by poorly hydrolyzable analogs of GTP, e.g. GTPyS... 

Synthesis of the transferrin receptor (TfR) and that of ferritin are reciprocally linked to cellular iron content. Specific untranslated sequences of the mRNAs for both proteins (named iron response elements) interact with a cytosolic protein sensitive to variations in levels of cellular iron (iron-responsive element-binding protein). When iron levels are high, cells use stored ferritin mRNA to synthesize ferritin, and the TfR mRNA is degraded. In contrast, when iron levels are low, the TfR mRNA is stabilized and increased synthesis of receptors occurs, while ferritin mRNA is apparently stored in an inactive form. This is an important example of control of expression of proteins at the translational level. 

The determination of quantity in complex mixtures is also vital in health care and medicine. We are all familiar with the medical examinations in which a sample of blood or urine is sent to a laboratory for analysis. The procedures used have been developed by chemists, and are performed by trained chemical technicians. The high level of automation achieved by the chemists who designed these analytical procedures has greatly reduced the costs of such analyses. Clinical analysis continues to be driven by a need for better methods to detect and measure important proteins, for example, that while present in tiny amounts are relevant to our health and well-being. 

Altogether, the identification of the coordinating residues in the endogenous hDAT Zn2+ binding site followed by the engineering artificial sites have defined an important series of structural constraints in this transporter. This includes not only a series of proximity relationships in the tertiary structure, but also secondary structure relationships. The data also provided information about the orientation of TM7 relative to TM8. A model of the TM7/8 microdomain that incorporates all these structural constraints is shown in Fig. 4 (36). The model is an important example of how structural inferences derived from a series of Zn2+ binding sites can provide sufficient information for at least an initial structural mapping of a selected protein domain. 

Lipid modified proteins are often attached to cell membranes. In many cases, they play crucial roles in the transduction of extracellular signals across the plasma membrane and into the nucleus. A particularly important example are the N-, K-, and H-Ras proteins. All Ras proteins terminate in a fame... 

While the majority of attention has focused on peptides contained within the nervous system, two other important methods for delivering peptides to the vicinity of the mast cell have been established (1) peptides produced and secreted by other cells of inflammation that may affect mast-cell function and (2) the local generation of mast-cell-active peptides by secreted enzymes acting on circulating protein precursors. Examples of the former include several, as yet ill-defined, peptide factors and cationic proteins from other immunocompetent cells [66-69], defined lymphokines such as the interleukin-1 [70] and interleukin-3 [71], and tumour necrosis factor [70], Examples of the latter include bradykinin [72] and a recently identified peptide produced by the action of acid proteinases on albumin [73, 74]. 

The latter compounds are of biological importance—cysteine, glutathione, and proteins are examples—and a novel antihypertensive drug, Captopril (Figure 9), also contains this functionality (59). Mercaptans can be prepared by the solvolysis of the thiolacetic acid adducts to olefins. 

Thus far, the discussion of G-proteins and effector enzymes has assumed that a ligand has engaged with its surface receptor. There is however, an important example of an alternative mechanism to activate an effector without the direct involvement of G-protein complex. NO is a local hormone, a neurotransmitter and part of the cell s armoury of oxidizing agents called free radicals. 

Second, albumin is a non-specific carrier protein. A wide range of chemically disparate compounds are bound loosely to albumin for transport through the blood stream. Important examples include calcium, bilirubin, drugs and free fatty acids. 

The primary source of variation in an assay system is usually the sample itself. This is the reason to have an assay in the first place. However, there may be variations in sample composition other than those toward which the assay is directed, and those variations may detract from the performance and reproducibility of the assay. Eliminating, or at least controlling, these influences can significantly improve resolution and sensitivity, as well as reproducibility. An important example is the ability of proteins to form stable complexes with a wide range of other solutes. Such complexes exhibit a range of aberrant retention behaviors that can confound interpretation of analytical results. 

Incorporation of biologically important molecules into LDHs has become of interest in recent years and materials such as DNA [189], ATP [190], amino acids or enzymes [191,192] and vitamins [193] can be stabilized in the interlayer space of LDHs. If enzymes and proteins, for example, can be immobilized in the interlayer galleries of LDHs, new types of selective catalysts (see Sect. 2.2) as well as new delivery systems and carrier materials can be expected. 

Based on our current understanding of ribosomal protein synthesis, several strategies have been developed to incorporate amino acids other than the 20 standard proteinogenic amino acids into a peptide using the ribosomal machinery . This allows for the design of peptides with novel properties. On the one hand, such a system can be used to synthesize nonstandard peptides that are important pharmaceuticals. In nature, such peptides are produced by nonribosomal peptide synthetases, which operate in complex pathways. On the other hand, non-natural residues are a useful tool in biochemistry and biophysics to study proteins. For example, incorporation of non-natural residues by the ribosome allows for site-specific labeling of proteins with spin labels for electron paramagnetic resonance spectroscopy, with... 

The substitution process permeates the whole realm of coordination chemistry. It is frequently the first step in a redox reaction and in the dimerization or polymerization of a metal ion, the details of which in many cases are still rather scanty (e.g. for Cr(III) ). An understanding of the kinetics of substitution can be important for defining the best conditions for a preparative or analytical procedure. Substitution pervades the behavior of metal or metal-activated enzymes. The production of apoprotein (demetalloprotein and the regeneration of the protein, as well as the interaction of substrates and inhibitors with metalloproteins are important examples. ... 

An interesting and important example of an animal poison is paralytic shellfish poison (PSP). This chemical, which is also known as saxitoxin and by several other names as well, is found in certain shellfish. But it is not produced by shellfish it is rather a metabolic product of certain marine microorganisms (Protista). These microorganisms are ingested by the shellfish as food, and their poison can remain behind in the shellfish s tissue. Paralytic shellfish poison is not a protein, but a highly complex organic chemical of most unusual molecular structure. 

The relaxivity enhancement associated with exchangeable protons in the second-coordination sphere of a Gd(III) complex is quite important in the supramolecular adducts of Gd(III)-based systems with proteins. For example, it has been reported that, besides water protons in the second-coordination... 

The new solvent systems (Section 5.1.7.1) were an important advance and opened the way for the solution segment synthesis of even larger and more complex proteins. For example, human midkine (121 residues) containing 5 disulfide bonds was assembled from Boc-(l -59)-OH and H-(60-121)-OBzl, which were not soluble in DMSO, but were readily soluble in CHCl/TFE (3 1) (Scheme 12).[441 The coupling was undertaken with a water-soluble car-bodiimide containing HOOBt and was complete in one hour. 

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