Understanding Active Sites: The Six Key Properties of Enzyme Functionality

previously we introduced the concept of the active site and we said that all the different types of enzymes down inside

our body and inside our cells have active sites so it turns out that just like all enzymes have similar properties

the active sites of enzymes also have important similar properties and this is what we're going to focus on in this

lecture we're going to discuss the six major properties of active sites and let's begin with property number one the

active site it's that location it's the three-dimensional region found on that enzyme that is responsible for

actually binding onto that substrate so inside the active site so this is our enzyme this is our active sites this

three-dimensional Kravis the three-dimensional crack in that enzyme is the active site and this active site

consists of the residues those amino acids that are responsible for binding onto the substrate and not only that

inside the active site we also have these catalytic groups these residues part of the enzyme that are responsible

for actually catalyzing that particular reaction and this leads us directly into property number two active sites are

responsible for stabilizing the transition state as well as forming and breaking the particular bonds involved

in that chemical biological reaction so inside the active side we have those residues responsible for actually

stabilizing and lowering the energy of the transition state and this is precisely what speeds up that particular

reaction in addition we have those catalytic groups that are responsible for stimulating the breaking of bonds

and the forming of bonds now property number three active sites create a micro environment so if we look in the

following diagram we have this active site and what the active site does is when it actually binds

to that substrate it essentially closes off ever so slightly and it creates this micro environment that is predominantly

nonpolar in fact the only time we're going to find water molecules inside the active site is when the water molecule

is actually a participant a reactant in that particular chemical reaction otherwise we'll never find the water

molecules inside the active site and that means the environment in the active site is nonpolar

now with this micro environment does is it brings the reactants very close together and it Orient's them in just

the right orientation for that specific reaction to actually take place and what it also does is it decreases the

likelihood that other reactions take place and that decreases the likelihood that unwanted products are actually

formed so active sites typically create nonpolar micro environments in which bonds can be formed and broken very

easily and unless water actually participates as a reactant in that biological reaction it is usually

excluded from that micro environment from that active site and this also helps prevent unwanted reactions now

property number four of active sites active sites actually only make up a very small portion a very small

component of that overall enzyme so even though the enzyme is usually relatively large that active site is actually quite

small compared to the overall structure and size of that particular enzyme the question is why well if we examine the

residues involved in active side those residues are usually found very far away apart from one another on that primary

sequence of the polypeptide chain and what that means is to bring those residues close together that entire

enzyme has to fold and form this particular three shape and to fold and bring those

residues that are far apart close together we have to fold in different ways and many times to basically form

the active side so it turns out the entire enzyme basically creates a scaffolding system that supports and

stabilizes that small section the active side that is actually used by the enzyme to catalyze that particular chemical

reaction so the active site is much smaller than the actual size of the enzyme so the remaining portion of the

enzyme acts to create stabilize and support the active site by bringing the residues that are far apart closer

together to basically catalyze the reaction and bind the substrate now in addition we can have other sites on the

enzyme outside of the active side that also play an important role in actually regulating the functionality of that

particular enzyme and these other sites are known as allosteric sites and we'll see many examples in the next several

lectures or in future lectures now on top of that these other portions of the enzyme can also interact with different

types of components found in a cell for example we have a variety of different types of proteins and enzymes found in a

cell membrane that actually bind onto that cell membrane and so these other sections of the enzyme can be

responsible for actually adhering and binding onto the cell machinery for example the membrane of the cell now

property number five of Enza of enzymes and the active sites of enzymes is that active sites typically bind substrates

reversibly via non covalent forces so in property number one and two we basically mentioned that inside the active site we

have these special residues the amino acids that contain the special sidechain groups that are responsible for actually

attaching and binding the substrate molecules and the bind that and the that takes place takes place via

non-covalent interactions such as hydrogen bonds such as hydrophobic interactions and Van der Waals forces so

non covalent electric forces such as hydrogen bonds van der Waals forces and the hydrophobic effect can all promote

the reversible binding between the active side and the substrate and what reversible binding basically means is

once the substrate binds on to that active side and once we convert the substrate to the product that product

will essentially release itself and move away from the active site it will not remain bound to that active site forever

that's what we mean by reversible binding now and this leads us directly into property six so recall from our

discussion on non covalent interactions we said that for non covalent interactions to actually be strong

enough and to actually be meaningful the distance between our bonds the distance between the molecules and atoms forming

the bonds actually has to be short enough and so what that means is in order for the substrate to actually get

close to the active side to get close enough to form those meaningful non covalent bonds the shape of that

substrate has to be complementary to that shape of the active site of the enzyme and that leads us to property six

active site active sites this should be active sites where is my marker so this should be active sites have structures

complimentary to their corresponding substrates so in order for the non covalent interactions between the

residues of the active site of the enzyme and the substrate to be meaningful and strong enough for them to

actually remain attached the distance between them must be short enough and this implies that the substrate must

fist must must fit snugly into the active site of that particular enzyme and this leads us into these two models

so these two models are generally used to basically describe the way that the binding between the substrate and the

active side of the enzyme actually takes place and although we still use the lock and key model it's really the induced

fit model that describes more correctly the way that our binding takes place so let's begin by discussing what we mean

by the lock and key model so lock and key simply means we have a key we have a lock and essentially when we place the

key into the lock we know that the shapes are complementary and that's why we have a

perfect fit between our lock and between our keys so in the lock and key model the substrate fits precisely and

perfectly into the active side to do to their complementary shapes so even before they actually bind what this

model tells us is the active side of the enzyme so the green structure is the enzyme this is the active side and this

is the substrate and notice that before the binding actually takes place this is complementary in structure to this

active site and so when they fit this simply moves into the active side and then they form those non covalent

interactions now according to our induced fit model the active side of that enzyme is not exactly complementary

to our substrate but when the binding actually takes place the enzyme actually conforms to the structure of that

substrate and so the enzymes active side basically changes shape ever so slightly it induces the shape and then once the

by Naik's place the active side basically conforms and takes the complementary shape of that particular

substrate molecule so in the induced fit model the shape of the enzymes active site is not exactly complementary

however upon binding of the substrate to the active site the binding causes the active site to become complementary to

the substrates so what the induced fit model basically tells us is when the binding

takes place the active site of that enzyme and the Sun and the substrate itself actually change shape ever so

slightly and they both conform into the shape in which each one is complementary to the others so the substrate becomes

complementary to active side and the active side becomes complementary to that particular substrate and it's due

and it's this induced fit model that actually describes correctly the way that the binding actually takes place

between the active side of the enzyme and the substrate