Sunday, September 23, 2012

Proteins: biochemical compounds

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function.
A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and aminogroups of adjacent amino acid residues. Sony VAIO PCG-3B1M Battery
The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the genetic code specifies 20 standard amino acids; however, in certain organisms the genetic code can include selenocysteine and—in certain archaea—pyrrolysine. Sony VAIO PCG-3C1T Battery
Shortly after or even during synthesis, the residues in a protein are often chemically modified by posttranslational modification, which alters the physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors. Sony VAIO PCG-3D1M Battery
Proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes.
Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms and participate in virtually every process within cells. Sony VAIO PCG-3G2M Battery
Many proteins are enzymes that catalyze biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, which form a system of scaffolding that maintains cell shape. Other proteins are important incell signaling, immune responses, cell adhesion, and the cell cycle. Sony VAIO PCG-5R1M Battery
Proteins are also necessary in animals' diets, since animals cannot synthesize all the amino acids they need and must obtain essential amino acids from food. Through the process of digestion, animals break down ingested protein into free amino acids that are then used in metabolism. Sony VAIO PCG-7141M Battery
Proteins may be purified from other cellular components using a variety of techniques such as ultracentrifugation,precipitation, electrophoresis, and chromatography; the advent of genetic engineering has made possible a number of methods to facilitate purification. Sony VAIO PCG-7143M Battery
Methods commonly used to study protein structure and function include immunohistochemistry, site-directed mutagenesis, nuclear magnetic resonance and mass spectrometry.
Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids. Sony VAIO PCG-7151M Battery
Allproteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, acarboxyl group, and a variable side chain are bonded. Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation. Sony VAIO PCG-7154M Battery
The side chains of the standard amino acids, detailed in the list of standard amino acids, have a great variety of chemical structures and properties; it is the combined effect of all of the amino acid side chains in a protein that ultimately determines its three-dimensional structure and its chemical reactivity. Sony VAIO PCG-7162M Battery
Theamino acids in a polypeptide chain are linked by peptide bonds. Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone.[3]
The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar. Sony VAIO PCG-7181M Battery
The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone.[4] The end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus, whereas the end with a free amino group is known as the N-terminusor amino terminus. Sony VAIO PCG-41112M Battery
The words proteinpolypeptide, and peptide are a little ambiguous and can overlap in meaning.Protein is generally used to refer to the complete biological molecule in a stable conformation, whereas peptideis generally reserved for a short amino acid oligomers often lacking a stable three-dimensional structure. Sony VAIO PCG-7153M Battery
However, the boundary between the two is not well defined and usually lies near 20–30 residues.[5] Polypeptidecan refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of a defined conformation.
Proteins are assembled from amino acids using information encoded in genes. Sony VAIO PCG-71312M Battery
Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination designates an amino acid, for example AUG (adenine-uracil-guanine) is the code for methionine. Sony VAIO PCG-7144M Battery
Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon.[6]Genes encoded in DNA are first transcribed into pre-messenger RNA (mRNA) by proteins such as RNA polymerase. Sony VAIO PCG-7191L Battery
Most organisms then process the pre-mRNA (also known as a primary transcript) using various forms of Post-transcriptional modification to form the mature mRNA, which is then used as a template for protein synthesis by the ribosome. In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid. Sony VAIO PCG-3C1M Battery
In contrast,eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm, whereprotein synthesis then takes place. The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second.[7] Sony VAIO PCG-3F1M Battery
The process of synthesizing a protein from an mRNA template is known as translation. The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. Sony VAIO PCG-3H1M Battery
The enzyme aminoacyl tRNA synthetase "charges" the tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain. Proteins are always biosynthesized from N-terminus to C-terminus.[6]
The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass, Sony VAIO PCG-3J1M Battery
which is normally reported in units of daltons (synonymous with atomic mass units), or the derivative unit kilodalton (kDa).Yeast proteins are on average 466 amino acids long and 53 kDa in mass.[5] The largest known proteins are the titins, a component of the muscle sarcomere, with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids.Sony VAIO PCG-8141M Battery
Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis, which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield. Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains. Sony VAIO PCG-8161M Battery
These methods are useful in laboratory biochemistry and cell biology, though generally not for commercial applications. Chemical synthesis is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure. Sony VAIO PCG-3C2M Battery
Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction.
Most proteins fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native conformation.Sony VAIO PCG-5N2M Battery
Although many proteins can fold unassisted, simply through the chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states.[13]Biochemists often refer to four distinct aspects of a protein's structure:[14]
Primary structure: the amino acid sequence. Sony VAIO PCG-5P1M Battery
Secondary structure: regularly repeating local structures stabilized by hydrogen bonds. The most common examples are the alpha helix, beta sheet and turns. Because secondary structures are local, many regions of different secondary structure can be present in the same protein molecule. Sony VAIO PCG-5S1M Battery
Tertiary structure: the overall shape of a single protein molecule; the spatial relationship of the secondary structures to one another. Tertiary structure is generally stabilized by nonlocal interactions, most commonly the formation of a hydrophobic core, but also through salt bridges, hydrogen bonds, disulfide bonds, and evenposttranslational modifications. Sony VAIO PCG-9Z1M Battery
The term "tertiary structure" is often used as synonymous with the term fold. The tertiary structure is what controls the basic function of the protein.
Quaternary structure: the structure formed by several protein molecules (polypeptide chains), usually calledprotein subunits in this context, which function as a single protein complex. Sony VAIO PCG-7171M Battery
Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations", and transitions between them are called conformational changes. Sony VAIO PCG-7186M Battery
Such changes are often induced by the binding of a substrate molecule to an enzyme's active site, or the physical region of the protein that participates in chemical catalysis. In solution proteins also undergo variation in structure through thermal vibration and the collision with other molecules. Sony VAIO PCG-81112M Battery
Proteins can be informally divided into three main classes, which correlate with typical tertiary structures:globular proteins, fibrous proteins, and membrane proteins. Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural, such as collagen, Sony VAIO PCG-31311M Battery
the major component of connective tissue, orkeratin, the protein component of hair and nails. Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane.
A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration, are called dehydrons. Sony VAIO PCG-8152M Battery
Discovering the tertiary structure of a protein, or the quaternary structure of its complexes, can provide important clues about how the protein performs its function. Common experimental methods of structure determination include X-ray crystallography and NMR spectroscopy, both of which can produce information at atomicresolution. Sony VAIO PCG-31111M Battery
However, NMR experiments are able to provide information from which a subset of distances between pairs of atoms can be estimated, and the final possible conformations for a protein are determined by solving adistance geometry problem. Sony VAIO PCG-61111M Battery
Dual polarisation interferometry is a quantitative analytical method for measuring the overall protein conformation and conformational changes due to interactions or other stimulus. Circular dichroism is another laboratory technique for determining internal beta sheet/ helical composition of proteins. Sony VAIO PCG-51112M Battery
Cryoelectron microscopy is used to produce lower-resolution structural information about very large protein complexes, including assembled viruses;[18] a variant known as electron crystallography can also produce high-resolution information in some cases, especially for two-dimensional crystals of membrane proteins. Sony VAIO PCG-51211M Battery
Solved structures are usually deposited in the Protein Data Bank (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of Cartesian coordinates for each atom in the protein.
Many more gene sequences are known than protein structures. Sony VAIO PCG-51212M Battery
Further, the set of solved structures is biased toward proteins that can be easily subjected to the conditions required in X-ray crystallography, one of the major structure determination methods. In particular, globular proteins are comparatively easy tocrystallize in preparation for X-ray crystallography. Sony VAIO PCG-41111M Battery
Membrane proteins, by contrast, are difficult to crystallize and are underrepresented in the PDB.[21]Structural genomics initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. Protein structure prediction methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined. Sony VAIO PCG-41111V Battery
Proteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes.[5] With the exception of certain types of RNA, most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia colicell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively. Sony VAIO PCG-61412V Battery
The set of proteins expressed in a particular cell or cell type is known as its proteome.
The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. Sony VAIO PCG-71112M Battery
This binding ability is mediated by the tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example,Sony VAIO PCG-81111V Battery
the ribonuclease inhibitor protein binds to humanangiogenin with a sub-femtomolar dissociation constant (<10 sup="sup">−15
 M) but does not bind at all to its amphibian homolog onconase(>1 M). Extremely minor chemical changes such as the addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; Sony VAIO PCG-81111V Battery
for example, the aminoacyl tRNA synthetase specific to the amino acid valinediscriminates against the very similar side chain of the amino acid isoleucine.[23]
Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of the same molecule, they can oligomerize to form fibrils; Sony VAIO PCG-81212M Battery
this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein–protein interactions also regulate enzymatic activity, control progression through the cell cycle, and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Sony VAIO PCG-81212V Battery
Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex signaling networks.[24] Importantly, as interactions between proteins are reversible, Sony VAIO PCG-51111M Battery
and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types. Sony VAIO VPCS13X9E/B battery
The best-known role of proteins in the cell is as enzymes, which catalyze chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism, as well as manipulating DNA in processes such as DNA replication, DNA repair, and transcription. Sony VAIO VPCS12V9E/B battery
Some enzymes act on other proteins to add or remove chemical groups in a process known as posttranslational modification. About 4,000 reactions are known to be catalyzed by enzymes.The rate acceleration conferred by enzymatic catalysis is often enormous—as much as 1017-fold increase in rate over the uncatalyzed reaction in the case of orotate Sony VAIO VPCS12V9E/B battery
decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme).
The molecules bound and acted upon by enzymes are called substrates. Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with the substrate, and an even smaller fraction—three to four residues on average—that are directly involved in catalysis. Sony VAIO VPCF13M8E/B battery
The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.
Dirigent proteins are members of a class of proteins which dictate the stereochemistry of a compound synthesized by other enzymes. Sony VAIO VPCF13Z0E/B battery
Many proteins are involved in the process of cell signaling and signal transduction. Some proteins, such as insulin, are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues. Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Sony VAIO VPCM13M1E/L battery
Many receptors have a binding site exposed on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell.[30] Sony VAIO VPCM13M1E/W battery
Antibodies are protein components of an adaptive immune system whose main function is to bind antigens, or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as plasma cells. Sony VAIO VPCF22M1E battery
Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.[31]
Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a multicellular organism. Sony VAIO VPCF11M1E/H battery
These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin, Sony VAIO VPCF13M0E/B battery
which transports oxygen from the lungs to other organs and tissues in all vertebrates and has closehomologs in every biological kingdom.[32] Lectins are sugar-binding proteins which are highly specific for their sugar moieties.Lectins typically play a role in biological recognition phenomena involving cells and proteins. Sony VAIO VPCYB2M1E battery
Receptors and hormones are highly specific binding proteins.
Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse. Sony VAIO VPCYB3V1E battery
Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions. Sony VAIO VGN-SR51MR Battery
Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Sony VAIO VPCY11M1E battery

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