Hemoglobin is a protein containing iron that facilitates the transport of oxygen in red blood cells. Almost all vertebrates contain hemoglobin,with the exception of the fish family Channichthyidae. Hemoglobin in the blood carries oxygen from the respiratory organs to the other tissues of the body,where it releases the oxygen to enable aerobic respiration which powers the animal's metabolism. A healthy human has 12 to 20 grams of hemoglobin in every 100 mL of blood. Hemoglobin is a metalloprotein,a chromoprotein,and globulin.
Structural biology,as defined by the Journal of Structural Biology,deals with structural analysis of living material at every level of organization.
Myoglobin is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin,myoglobin has a higher affinity for oxygen and does not have cooperative binding with oxygen like hemoglobin does. Myoglobin consists of non-polar amino acids at the core of the globulin,where the heme group is non-covalently bounded with the surrounding polypeptide of myoglobin. In humans,myoglobin is found in the bloodstream only after muscle injury.
Dihydrofolate reductase,or DHFR,is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid,using NADPH as an electron donor,which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In humans,the DHFR enzyme is encoded by the DHFR gene. It is found in the q14.1 region of chromosome 5.
Cooperative binding occurs in molecular binding systems containing more than one type,or species,of molecule and in which one of the partners is not mono-valent and can bind more than one molecule of the other species. In general,molecular binding is an interaction between molecules that results in a stable physical association between those molecules.
Metalloprotein is a generic term for a protein that contains a metal ion cofactor. A large proportion of all proteins are part of this category. For instance,at least 1000 human proteins contain zinc-binding protein domains although there may be up to 3000 human zinc metalloproteins.
Phenylalanine hydroxylase (PAH) (EC 1.14.16.1) is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PAH is one of three members of the biopterin-dependent aromatic amino acid hydroxylases,a class of monooxygenase that uses tetrahydrobiopterin (BH4,a pteridine cofactor) and a non-heme iron for catalysis. During the reaction,molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate. In humans,mutations in its encoding gene,PAH,can lead to the metabolic disorder phenylketonuria.
Sir John Cowdery Kendrew,was an English biochemist,crystallographer,and science administrator. Kendrew shared the 1962 Nobel Prize in Chemistry with Max Perutz,for their work at the Cavendish Laboratory to investigate the structure of haem-containing proteins.
In biochemistry and molecular biology,a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may include other proteins,enzyme substrates,second messengers,hormones,or allosteric modulators. The binding event is often,but not always,accompanied by a conformational change that alters the protein's function. Binding to protein binding sites is most often reversible,but can also be covalent reversible or irreversible.
In molecular biology,an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure,typically in the absence of its macromolecular interaction partners,such as other proteins or RNA. IDPs range from fully unstructured to partially structured and include random coil,molten globule-like aggregates,or flexible linkers in large multi-domain proteins. They are sometimes considered as a separate class of proteins along with globular,fibrous and membrane proteins.
Allosteric enzymes are enzymes that change their conformational ensemble upon binding of an effector which results in an apparent change in binding affinity at a different ligand binding site. This "action at a distance" through binding of one ligand affecting the binding of another at a distinctly different site,is the essence of the allosteric concept. Allostery plays a crucial role in many fundamental biological processes,including but not limited to cell signaling and the regulation of metabolism. Allosteric enzymes need not be oligomers as previously thought,and in fact many systems have demonstrated allostery within single enzymes. In biochemistry,allosteric regulation is the regulation of a protein by binding an effector molecule at a site other than the enzyme's active site.
Frederic Middlebrook Richards,commonly referred to as Fred Richards,was an American biochemist and biophysicist known for solving the pioneering crystal structure of the ribonuclease S enzyme in 1967 and for defining the concept of solvent-accessible surface. He contributed many key experimental and theoretical results and developed new methods,garnering over 20,000 journal citations in several quite distinct research areas. In addition to the protein crystallography and biochemistry of ribonuclease S,these included solvent accessibility and internal packing of proteins,the first side-chain rotamer library,high-pressure crystallography,new types of chemical tags such as biotin/avidin,the nuclear magnetic resonance (NMR) chemical shift index,and structural and biophysical characterization of the effects of mutations.
Type II topoisomerases are topoisomerases that cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of ATP,unlike Type I topoisomerase. In this process,these enzymes change the linking number of circular DNA by ±2. Topoisomerases are ubiquitous enzymes,found in all living organisms.
John Kuriyan is the dean of basic sciences and a professor of biochemistry at Vanderbilt University School of Medicine. He was formerly the Chancellor's Professor at the University of California,Berkeley in the departments of molecular and cell biology (MCB) and chemistry,a faculty scientist in Berkeley Lab's physical biosciences division,and a Howard Hughes Medical Institute investigator. He is a member of the National Academy of Sciences and he has also been on the Life Sciences jury for the Infosys Prize in 2009,2019 and 2020.
Morpheeins are proteins that can form two or more different homo-oligomers,but must come apart and change shape to convert between forms. The alternate shape may reassemble to a different oligomer. The shape of the subunit dictates which oligomer is formed. Each oligomer has a finite number of subunits (stoichiometry). Morpheeins can interconvert between forms under physiological conditions and can exist as an equilibrium of different oligomers. These oligomers are physiologically relevant and are not misfolded protein;this distinguishes morpheeins from prions and amyloid. The different oligomers have distinct functionality. Interconversion of morpheein forms can be a structural basis for allosteric regulation,an idea noted many years ago,and later revived. A mutation that shifts the normal equilibrium of morpheein forms can serve as the basis for a conformational disease. Features of morpheeins can be exploited for drug discovery. The dice image represents a morpheein equilibrium containing two different monomeric shapes that dictate assembly to a tetramer or a pentamer. The one protein that is established to function as a morpheein is porphobilinogen synthase,though there are suggestions throughout the literature that other proteins may function as morpheeins.
A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred. Usually this common ancestry is inferred from structural alignment and mechanistic similarity,even if no sequence similarity is evident. Sequence homology can then be deduced even if not apparent. Superfamilies typically contain several protein families which show sequence similarity within each family. The term protein clan is commonly used for protease and glycosyl hydrolases superfamilies based on the MEROPS and CAZy classification systems.
S. Samar Hasnain FInstP,FRSC,is the inaugural Max Perutz professor of Molecular Biophysics at the University of Liverpool. In 1991 he became a Fellow of the Institute of Physics and in 2002 he became a Fellow of the Royal Society of Chemistry. In 1997 he became a Fellow of the Third World Academy of Sciences. He became Foreign Fellows of Pakistan Academy of Sciences in 2017.
Alice Vrielink is a structural biologist and Professor of Structural Biology in the School of Molecular Sciences at the University of Western Australia. She is known for her work determining the structures of macromolecules such as enzymes and nucleic acids.
