Biomedical Engineering Reference
In-Depth Information
4 Functional Discrimination of Membrane Proteins
In this section, we focus on the databases and methods developed for the classifica-
tion of membrane proteins based on their functions. Specifically, we describe the
methods to discriminate transporter proteins from other globular and membrane
proteins along with the classification of transporters based on different classes and
families including channels and pores.
4.1 Databases for Membrane Transporters and Functionally
Important Residues in Membrane Proteins
Saier et al. [
76
] developed the Transporter Classification Database (TCDB), which
contains sequence, structural, functional, and evolutionary information about trans-
port systems from a variety of living organisms, based on the International Union of
Biochemistry and Molecular Biology-approved transporter classification (TC) sys-
tem. It is a curated repository for factual information compiled largely from
published references. It uses a functional/phylogenetic system of classification,
and currently encompasses about 5,000 representative transporters and putative
transporters in more than 500 families.
Transport systems are classified on the basis of five components such as (1)
transporter class (i.e., channel, carrier, primary active transporter, or group
translocator), (2) transporter subclass which in the case of primary active transporters
refers to the energy source used to drive transport, (3) transporter family, (4)
subfamily, and (5) substrate or range of substrates transported. The browsing options
available in TCDB are illustrated in Fig.
5
. It also has the facility to retrieve data with
several search options. TCDB is freely accessible at
http://www.tcdb.org
.
Gromiha et al. [
77
] developed the database TMFunction, which is a collection of
experimentally observed functional residues in membrane proteins reported in the
literature. Each entry includes the numerical values for the parameters IC50
(measure of the effectiveness of a compound in inhibiting biological function),
Vmax (maximal velocity of transport), relative activity of mutants with respect to
wild type protein, binding affinity, dissociation constant, etc., which are important
for understanding the sequence-structure-function relationship of membrane
proteins. In addition, they have provided information about name and source of
the protein, Uniprot and PDB codes, mutational and literature information. Further-
more, TMFunction is linked with related databases and other resources. A web
interface has been set up with different search and display options so that users have
the ability to get the data in several ways. TMFunction is freely available at
http://
tmbeta-genome.cbrc.jp/TMFunction/
. The usage of TMFunction is illustrated with
the following example. The data obtained for the function “drug” and single
mutants is shown in Fig.
6a
. The terms: entry, protein, Uniprot ID, mutation,
