Proteins and enzymes

The building blocks of proteins and enzymes are molecules formed by carboxyl acids attached to amino groups (–NH₂), known as amino acids. Most protein structures consist of combinations of only about twenty of the most commonly found amino acids.

Amino acids bind to each other to form peptides and proteins. Conventionally, the term protein is used to designate chains of several peptides, known as polypeptides, with a molecular weight higher than thousands of Daltons. Peptides with a biological function go in length from dipeptides and tripeptides, up to polymers with thousands of Daltons.

Most proteins have well-defined structures and their specific biological functions depend upon the correct conformation of the molecular structure. For instance, the majority of soluble proteins of an organism, such as blood proteins, have globular structures, like small eggs. Some proteins are fiber-like and are associated in bundles, forming fibrils such as those of wool and hair. Myosin, the protein that makes muscles contract, has both globular and fibrous elements in its structure; whereas collagen, the protein of connective tissues, is constituted by three triple helices of fibrils that form super structures in the shape of a fibrous rope. Collagen represents one third of all proteins of the human body and together with elastin is responsible for both cohesion and elasticity of tissues.

Every enzyme is also a protein. Enzymes are proteins that function as catalysts of biochemical reactions. Most physiological activities in organisms are mediated by enzymes, from unicellular life forms to mammals. Enzymes speed up chemical reactions, allowing organic systems to reach equilibrium in a faster pace. For instance, every phase of the cell cycle is controlled by enzymes that alternately inhibit or stimulate specific cellular activities as well as gene expression or repression, hence affecting the time of specific physiological activities within each phase of the cell cycle. Enzymes are highly selective in their activities, with each enzyme acting over a specific substrate or group of substrates. Substrate is a term designating any molecule that suffers enzymatic action, whether being activated or inhibited.

The main property of catalyst molecules is that they are not altered by the chemical reactions they induce, although some rare exceptions are known where some enzymes are inactivated by the reactions they catalyze. Enzymatic catalysis involves the formation of protein complexes between substrate and enzyme, where the amount of enzymes is generally much greater than the amount of substrate.

Some families of enzymes play an important role during the process of DNA replication. For example, when DNA synthesis activates, helicases break hydrogen bridges and some topoisomerases separate the two DNA strands. DNA-polymerases synthesize the fragments of the new DNA strand, while topoisomerase III does the proofreading of the transcribed sequences, eliminating those containing errors. Ribonuclease H removes RNA sequences from polymers containing complexed RNA/DNA, and DNA-ligase unites the newly transcribed fragments, thus forming the new DNA strand.

In the last decade, researchers discovered that many proteins involved in intracellular communication are structured in a modular way. In other words, they are constituted by relatively short amino acid sequences of about 100 amino acids, and have the basic role of connecting one protein to another. Some proteins of such signaling pathways are entirely comprised of connecting modules and deprived of enzymatic activity. These non-enzymatic modules are termed protein dominium or protein modules, and they help enzymes in the transmission of signals to the cell nucleus in an orderly and controlled way. Proteins containing only connecting (or binding) modules, such as SH2 and SH3, act as important molecular adaptors to other proteins. While one of its modules binds to a signaling complex, such as a transmembrane tyrosine-kinase receptor, other binding modules permit the docking of other proteins that, once complexed, amplifies the signal to the nucleus. Such adaptor proteins also allow the cell to utilize certain enzymes that otherwise would not be activated in a given signaling pathway. The structure of adaptor proteins also displays binding sites that connect to DNA, where they recognize specific nucleotide sequences of a given gene, thus inducing transcription . In this case, the only enzyme in the cascade of signals to the nucleus is the receptor in the surface of the cell, and all the events that follow occur through the recognition among proteins and through the protein recognition of a locus in DNA.

Proteins are encoded by genes. A gene usually encodes a nucleotide sequence that can be first transcribed in pre-messenger RNA, and then read and translated on the ribosomes into a group of similar proteins with different lengths and functions, known as protein isoforms. A single polypeptide may be translated and then cut by enzymes into different proteins of variable lengths and molecular weights.

During transcription, the non-coding DNA sequences (introns) are cut off, and the coding sequences (exons) are transcribed into pre-messenger RNA, which in turn is spliced to a continuous stretch of exons before protein translation begins. The spliced stretch subdivides in codons, where any of the four kinds of nucleotide may occupy one or more of the three positions, and each triplet codes for one specific amino acid. The sequence of codons is read on the ribosomes, three nucleotides at a time. The order of codons determine the sequence of amino acids in the protein molecule that is formed.

Introns may have a regulatory role of either the splicing or the translational process, and may even serve as exons to other genes. After translation, proteins may also undergo biochemical changes, a process known as post-translation processing. They may be either cut by enzymes or receive special bonds, such as disulfide bridges, in order to fold into a functional structure.

See also Biochemistry; Cell cycle (eukaryotic), genetic regulation of; Cell cycle (prokaryotic), genetic regulation of; DNA (Deoxyribonucleic acid); Transcription; Translation