Protein structure - Pharmaceutical Biotechnology: Concepts and Aapplications - page 15

Protein structure

2.1 Introduction

Almost all products of modern pharmaceutical biotechnology, be they on the market or likely to gain
approval in the short to intermediate term, are protein based. As such, an understanding of protein
structure is central to this topic. A comprehensive treatment of the subject would easily constitute a
topic on its own, and many such publications are available. The aim of this chapter is to provide a basic
overview of the subject in order to equip the reader with a knowledge of protein science suffi cient to un-
derstand relevant concepts outlined in the remaining chapters of this topic. The interested reader is also
referred to the 'Further reading' section, which lists several excellent specialist publications in the fi eld.
Much additional information may also be sourced via the web sites mentioned within the chapter.

2.2 Overview of protein structure

Proteins are macromolecules consisting of one or more polypeptides ( Table 2.1). Each polypeptide
consists of a chain of amino acids linked together by peptide (amide) bonds. The exact amino
acid sequence is determined by the gene coding for that specifi c polypeptide. When synthesized,
a polypeptide chain folds up, assuming a specifi c three-dimensional shape (i.e. a specifi c confor-
mation) that is unique to it. The conformation adopted is dependent upon the polypeptide's amino
acid sequence, and this conformation is largely stabilized by multiple, weak non-covalent interac-
tions. Any infl uence (e.g. certain chemicals and heat) that disrupts such weak interactions results
in disruption of the polypeptide's native conformation, a process termed denaturation. Denatura-
tion usually results in loss of functional activity, clearly demonstrating the dependence of protein
function upon protein structure. A protein's structure currently cannot be predicted solely from its
amino acid sequence. Its conformation can, however, be determined by techniques such as X-ray
diffraction and nuclear magnetic resonance (NMR) spectroscopy.
Proteins are sometimes classifi ed as 'simple' or 'conjugated'. Simple proteins consist exclu-
sively of polypeptide chain(s) with no additional chemical components present or being required
for biological activity. Conjugated proteins, in addition to their polypeptide components(s),