Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

PROTEIN FUNCTION
135
ligand
binding
site
noncovalent bonds
(B)
Figure 3–37 The selective binding of a
protein to another molecule. Many weak
bonds are needed to enable a protein
to bind tightly to a second molecule, or
ligand. A ligand must therefore fit precisely
into a protein’s binding site, like a hand
into a glove, so that a large number of
noncovalent bonds form between the
protein and the ligand. (A) Schematic;
(B) space-filling model. (PDB code: 1G6N.)
(A)
protein
The region of a protein that associates with a ligand, known as the ligand’s binding
site, usually consists of a cavity in the protein surface formed by a particular
arrangement of amino acids. These amino acids can belong to different portions
of the polypeptide chain that MBoC6 are brought m3.36/3.33 together when the protein folds (Figure
3–38). Separate regions of the protein surface generally provide binding sites for
different ligands, allowing the protein’s activity to be regulated, as we shall see
later. And other parts of the protein act as a handle to position the protein in the
cell—an example is the SH2 domain discussed previously, which often moves a
protein containing it to particular intracellular sites in response to signals.
Although the atoms buried in the interior of the protein have no direct contact
with the ligand, they form the framework that gives the surface its contours and
its chemical and mechanical properties. Even small changes to the amino acids in
the interior of a protein molecule can change its three-dimensional shape enough
to destroy a binding site on the surface.
The Surface Conformation of a Protein Determines Its Chemistry
The impressive chemical capabilities of proteins often require that the chemical
groups on their surface interact in ways that enhance the chemical reactivity of
one or more amino acid side chains. These interactions fall into two main categories.
First, the interaction of neighboring parts of the polypeptide chain may restrict
the access of water molecules to that protein’s ligand-binding sites. Because water
molecules readily form hydrogen bonds that can compete with ligands for sites
Figure 3–38 The binding site of a
protein. (A) The folding of the polypeptide
chain typically creates a crevice or cavity on
the protein surface. This crevice contains a
set of amino acid side chains disposed in
such a way that they can form noncovalent
bonds only with certain ligands. (B) A
close-up of an actual binding site, showing
the hydrogen bonds and electrostatic
interactions formed between a protein and
its ligand. In this example, a molecule of
cyclic AMP is the bound ligand.
amino acid
side chains
(A)
unfolded protein
FOLDING
binding site
folded protein
H
C
O N
H
C
H
C
(CH 2 ) 3
NH
(B)
arginine
serine
CH 2
hydrogen bond
O
H
5′
O O
cyclic AMP
P O
+
C NH 2 O O
3′
NH 2 N N
O
H
N H N
N
O
C O_
electrostatic
attraction
CH 2
CH glutamic
2
acid
C
serine
H
H
O CH C
2
H
N
H
H O threonine
CH
H 3 C C
H
H