DNA structure

DNA is usually a double-helix and has two strands running in opposite directions. (There are some
examples of viral DNA which are single-stranded). ach chain is a polymer of subunits called nucleotides
(hence the name polynucleotide).
ach strand has a bac!bone made up of (deoxy-ribose) sugar molecules lin!ed together by phosphate
groups. The "# $ of a sugar molecule is connected through a phosphate group to the %# $ of the next sugar.
This lin!age is also called "#-%# phosphodiester lin!age. All DNA strands are read from the %# to the "# end
where the %# end terminates in a phosphate group and the "# end terminates in a sugar molecule.
What is RNA?
Ribonucleic acid, or RNA is one of the three major biological macromolecules that are essential
for all known forms of life (along with DNA and proteins). A central tenant of molecular biology
states that the flow of genetic information in a cell is from DNA through RNA to proteins !DNA
makes RNA makes protein". #roteins are the workhorses of the cell$ they play leading roles in
the cell as en%ymes, as structural components, and in cell signaling, to name just a
few. DNA(deo&yribonucleic acid) is considered the !blueprint" of the cell$ it carries all of the
genetic information re'uired for the cell to grow, to take in nutrients, and to propagate. RNA(in
this role(is the !DNA photocopy" of the cell. )hen the cell needs to produce a certain protein, it
acti*ates the protein+s gene(the portion of DNA that codes for that protein(and produces
multiple copies of that piece of DNA in the form of messenger RNA, or mRNA. ,he multiple
copies of mRNA are then used to translate the genetic code into protein through the action of
the cell+s protein manufacturing machinery, the ribosomes. ,hus, RNA e&pands the 'uantity of a
gi*en protein that can be made at one time from one gi*en gene, and it pro*ides an important
control point for regulating when and how much protein gets made.
-or many years RNA was belie*ed to ha*e only three major roles in the cell(as a DNA
photocopy (mRNA), as a coupler between the genetic code and the protein building blocks
(tRNA), and as a structural component of ribosomes (rRNA). .n recent years, howe*er, we ha*e
begun to reali%e that the roles adopted by RNA are much broader and much more interesting.
)e now know that RNA can also act as en%ymes (called ribo%ymes) to speed chemical
reactions. .n a number of clinically important *iruses RNA, rather than DNA, carries the *iral
genetic information. RNA also plays an important role in regulating cellular processes(from cell
di*ision, differentiation and growth to cell aging and death. Defects in certain RNAs or the
regulation of RNAs ha*e been implicated in a number of important human diseases, including
heart disease, some cancers, stroke and many others.
What Foods Are in the Protein Foods Group?
All foods made from meat, poultry, seafood, beans and peas, eggs, processed soy products,
nuts, and seeds are considered part of the #rotein -oods /roup. 0eans and peas are also part
of the 1egetable /roup. -or more information on beans and peas, see 0eans and #eas Are
2ni'ue -oods.
3elect a *ariety of protein foods to impro*e nutrient intake and health benefits, including at least
4 ounces of cooked seafood per week. 5oung children need less, depending on their age and
calorie needs. ,he ad*ice to consume seafood does not apply to *egetarians. 1egetarian
options in the #rotein -oods /roup include beans and peas, processed soy products, and nuts
and seeds. 6eat and poultry choices should be lean or low7fat.
Introduction
&roteins are macromolecules (heteropolymers) made up from '( different )amino acids* also referred
to as residues. +elow about ,( residues the term peptide is fre-uently used. A certain number of residues
is necessary to perform a particular biochemical function* and around ,(-%( residues appears to be the
lower limit for a functional domain si.e. &rotein si.es range from this lower limit to several hundred
residues in multi-functional proteins. /ery large aggregates can be formed from protein subunits* for
example many thousand actin molecules assemble into a an actin filament. )arge protein complexes with
0NA are found in the ribosome particles* which are in fact #ribo.ymes#.
Amino acids
The basic structure of an amino acid is -uite simple. 0 denotes any one of the '( possible side chains
(see table below). 1e notice that the $-atom has , different ligands (the 2 is omitted in the drawing)
and is thus chiral. An easy tric! to remember the correct )-form is the $30N-rule4 when the $-atom is
viewed with the 2 in front* the residues read 5$3-0-N5 in a cloc!wise direction.
The polypeptide chain
Two amino acids are combined in a condensation reaction. Notice that the peptide bond is in fact planar
due to the delocali.ation of the electrons. The se-uence of the different amino acids is considered
theprimary structure of the peptide or protein. $ounting of residues always starts at the N-terminal end
(N2'-group).
Secondary structure elements
The polypeptide chain of a protein seldom forms 6ust a random coil. 0emember that proteins have either a
chemical (en.ymes) or structural function to fulfill. 2igh specificity re-uires an intricate arrangement of
"-dimensional interactions and therefore a defined conformation of the polypeptide chain. 7n fact* some
neurodegenerative diseases li!e 2untington#s may be related to random coil formation in certain proteins.
The two most common secondary structure arrangements are the right-handed -helix and the -sheet*
which can be connected into a larger tertiary structure (or fold) by turns and loops of a variety of types.
These two secondary structure elements satisfy a strong hydrogen bond networ! within the geometric
constraints of the bond angles * and . The -sheets can be formed by parallel or* most common*
antiparallel arrangement of individual -strands.
Mutations
Mutations, or changes in the DNA sequence, will often lead to changes in the amino acid
sequence of the resulting polypeptide. If the structure of the protein changes, then the function
will also change.
Mutations can come from several sources, including environmental mutagens and replication
errors. In colloquial terms, mutations are not considered good. However, not all changes are
harmful. Some may e neutral, while others may e eneficial. It is these eneficial mutations
that can lead to evolution of species !see "hapter #$%.
Mutations fall into three main categories !see &igure '.(%)
8 ase pair sustitutions) *hen a gene is altered in one nucleotide in the
sequence, then only one amino acid in the protein may e altered !ut
rememer the degeneracy of the code and the wole rules) a nucleotide
change may not result in a change in the amino acid%. +his single amino
acid difference may result in a fatal disease, alter the function of the
protein !thus creating a new variation or trait) see "hapter ,-%, or it may
not affect the function of the protein at all. However, if a codon specifying
an amino acid is changed to a termination codon, the polypeptide will not
e translated eyond that point. +his truncated transcript will, in all
li.elihood, not function properly.
,he heli&7loop7heli& (9:9) family of transcriptional regulatory proteins are key players in a wide
array of de*elopmental processes. ;*er <=> 9:9 proteins ha*e been identified to date in
organisms ranging from the yeast Saccharomyces cerevisiae to humans. 3tudies in Xenopus
laevis, Drosophila melanogaster, and mice ha*e con*incingly demonstrated that 9:9 proteins
are intimately in*ol*ed in de*elopmental e*ents such as cellular differentiation, lineage
commitment, and se& determination. .n yeast, 9:9 proteins regulate se*eral important
metabolic pathways, including phosphate uptake and phospholipid biosynthesis. .n multicellular
organisms, 9:9 factors are re'uired for a multitude of important de*elopmental processes,
including neurogenesis, myogenesis, hematopoiesis, and pancreatic de*elopment. ,he purpose
of this re*iew is to e&amine the structure and functional properties of 9:9 proteins.
A number of eukaryotic proteins, which probably are sequence specific DNA-
binding proteins that act as transcription factors, share a conserved domain of 40 to
0 amino acid residues! "t has been proposed #$%"D& '4()((0* that this domain is
formed of two amphipathic helices +oined by a variable length linker region that
could form a loop! ,his -heli.-loop-heli.- /0102 domain mediates protein
dimeri3ation and has been found in the proteins listed below #$%"D& 4'45)6*!
%ost of these proteins have an e.tra basic region of about 4 amino acid residues
that is ad+acent to the 010 domain and specifically binds to DNA! ,hey are refered
as basic heli.-loop-heli. proteins /b0102, and are classified in two groups& class A
/ubiquitous2 and class 7 /tissue-specific2! %embers of the b010 family bind
variations on the core sequence -8ANN,9-, also refered to as the :-bo. motif! ,he
homo- or heterodimeri3ation mediated by the 010 domain is independent of, but
necessary for DNA binding, as two basic regions are required for DNA binding
activity! ,he 010 proteins lacking the basic domain /:mc, "d2 function as negative
regulators, since they form heterodimers, but fail to bind DNA! ,he hairy-related
proteins /hairy, :/spl2, deadpan2 also repress transcription although they can bind
DNA! ,he proteins of this subfamily act together with co-repressor proteins, like
groucho, through their 8-terminal motif ;<$;!
The Chemistry of Amino Acids
Amino acids play central roles both as building bloc!s of proteins and as intermediates in metabolism.
The '( amino acids that are found within proteins convey a vast array of chemical versatility. The precise
amino acid content* and the se-uence of those amino acids* of a specific protein* is determined by the
se-uence of the bases in the gene that encodes that protein. The chemical properties of the amino acids of
proteins determine the biological activity of the protein. &roteins not only cataly.e all (or most) of the
reactions in living cells* they control virtually all cellular process. 7n addition* proteins contain within
their amino acid se-uences the necessary information to determine how that protein will fold into a three
dimensional structure* and the stability of the resulting structure. The field of protein folding and stability
has been a critically important area of research for years* and remains today one of the great unsolved
mysteries. 7t is* however* being actively investigated* and progress is being made every day.
As we learn about amino acids* it is important to !eep in mind that one of the more important reasons to
understand amino acid structure and properties is to be able to understand protein structure and properties.
1e will see that the vastly complex characteristics of even a small* relatively simple* protein are a
composite of the properties of the amino acids which comprise the protein.
Types of volution
1hen we examine evolution as a process* we see certain patterns. 7t is helpful to
discuss evolution in terms of these patterns to answer -uestions and ma!e comparisons.
These patterns include4
8 divergent evolution4 This process refers to what is normally thought of as
evolution* and what we have been discussing thus far. Divergent evolution
occurs when individuals from one population evolve differently. This* as
discussed above* can lead to speciation. 9or example* the brown bear and
the polar bear had a common ancestor. :igration of the bears* leading to
geographic isolation* resulted in adaptation to different environments.
Divergent evolution often results in individuals having homologous
structures* structures that have been adapted differently to perform
different functions. 9or example* the forelimbs in vertebrates evolved into
arms (humans)* wings (bats) and fins (whales).
8 convergent evolution41hen environments are similar or identical* the
same selective pressures will be placed on the organisms that live in these
environments. Therefore* different species in one environment (or two
similar environments) will evolve similar structures to function in the
environment. These structures are called analogous structures. 3ne
stri!ing example of this is seen in shar!s (fish)* whales (mammals) and
penguins (birds)4 although very distantly related* all have developed
similar structures (fins) that allow them to function in the same
environment (the ocean).
Aminoglycosides
Aminoglycosides are a group of antibiotics in which amino sugars
are lin!ed by glycoside bonds. Aminoglycoside antibiotics* such as
streptomycin and gemamicin, interfere with the initial steps of protein
synthesis by changing the shape of the "(; portion of the <(;
pro!aryotic ribosome. This interference causes the genetic code of
the m0NA to be read incorrectly. They were among the first antibiotics
to have significant activity against gram-negative bacteria.
&robably the best-!nown aminoglycoside is streptomycin, which
was discovered in =>,,. ;treptomycin is still used as an alternative
drug in the treatment of tuberculosis* but rapid development of
resistance and serious toxic effcxts have diminished its usefulness.
Aminoglycosides can affect hearing by causing permanent
damage to the auditory nerve* and damage to the !idneys has also
been reported. As a result* their usc has been declining. Neomycirl is
present in many nonprescription topical preparations. Gentamicin
(spelled with an 5i5 to reflect its source* the filamentous bacterium
Micromonospora) is especially useful against Pseudomonas infcxtions.
&seudomonads are a ma6or problem for persons suffering
from cystic fibrosis. The aminoglycoside tobramycin is administered
in an aerosol to help control infections that occur in patients