BIOINORGANIC CHEMISTRY A Short Course Second Edition

CALCIUM-DEPENDENT MOLECULES 303

Before continuing the discussion of calmodulin ’ s properties and activities
in vivo, it is important to note that excerpts from the careful reading of primary
sources have been used to inform readers on this topic. These sources range
in age from the mid - to late 1980s to late 2005 and encompass the work of
many different laboratories. Over these 20+ years, methods and terminology
have changed substantially. Terminology will create the greatest sources of
confusion in the following discussion. For instance, one fi nds references to
calmodulin ’ s helical domains using the letters A through H but also Roman
numerals I through VIII. In one 2002 paper, the authors designate the D and
E central linker helices as both having the Roman numeral IV.^91 In this system,
calmodulin ’ s helical domains have numerals I through VII. Fortunately, the
numbering system for calmodulin amino acid residues 1 – 148 seems to be
constant over all sources. Another numbering system creating confusion will
arise in the discussions of target enzyme peptide binding domains as they bond
to calmodulin. At least two numbering systems are used to identify the peptide
residue sequence in the discussions that follow, and these are outlined in Table
6.9. This author has tried to address the confusion in the terminology used, but
readers consulting the primary sources referenced here, or newer sources in
calmodulin ’ s continuing story, should expect to spend time relating one author ’ s
terminology to that of another.

6.3.2.2 Calmodulin Structure by X -Ray and NMR. Babu and co - workers
published the fi rst X - ray crystallographic structure of Ca 2+ - saturated mam-
malian calmodulin in 1986 (PDB ascension number 3CLN).^71 As can be seen
in Figure 6.21 , the molecule is dumbbell - shaped, with an overall length of 65 Å.
There are two two - EF - hand domains or lobes — N - terminal, residues 5 – 73 and
C - terminal, residues 74 – 148 — connected by a central seven - turn α - helix. The
center part of the connecting helix is unwound between residues asp78 and

Figure 6.21 Calmodulin dumbbell shape (PDB: 3CLN). Visualized using Cambridge-
Soft Chem3D Ultra 10.0 with notations in ChemDraw Ultra 10.0. (Printed with permis-
sion of CambridgeSoft Corporation.)

N-terminal end

C-terminal end

asp78

ser81

Calmodulin PDB: 3CLN

Ca2+

Ca2+

Ca2+

Ca2+