Conformationof 'Eyco(-L-Pro-Gly-)3 And Its Ca2' And Mg2 Complexes (Page 2 of 4) in pdf

Proc. NatL Acad. Sci. USA 79 (1982)

FIG. 1. Stereo view of (PG)3 molecule crystallized from a

polar

medium. The a-carbons are numbered 1-6. The structure is asymmetric with

one Gly-Pro peptide bond (4-5) in the

cis configuration. The carbonyls

the

first and fourth residues are linked by a

hydrogen-bonded

water

bridge

involving three water molecules

(W1-3).

The water molecule W2

sits

on a twofold axis.

or internal hydrogen bonds (11, 12) characteristic ofcyclic hexa-

peptides. Five of the peptide bonds in the ring occur in the usual

trans conformation, and one ofthe Gly-Pro bonds is cis. Though

cyclic di- and tripeptides can be fbimed only with all peptide

links cia (13, 14), in larger peptides the ring closure can be

achieved with all trans peptide units. Even though cia peptides

have been noted to occur in many other cyclic peptides (15-19),

they are very rarely observed

in the crystallographic structures

of cyclic hexapeptides. For (PG)3 such an asymmetric structure

has indeed been suggested earlier by Blout and colleagues (7).

Another interesting feature of the crystal structure is the for-

mation of a dimer about the crystallographic twofold axis by

strong N-H--O hydrogen bonds between N2 and 02 with a

nitrogen--oxygen distance of 2.

This asymmetric conformer

is stabilized by hydrogen bonds involving three water molecules

linking carbonyls 01 and

(Fig.

1). The main chain as well

as the proline ring torsion angles of this structure are given in

Table 2.

Peptide Ca Complex. With calcium, (PG)3 forms a 1:2 com-

plex

such that the

Ca"+

is sandwiched

between two peptide

molecules (Figs. 2 and 3). The peptide sandwich sits on the

threefold axis of the unit cell, -and thus .the crystal structure in-

deed uses the threefold symmetry of the molecular complex.

One of the

perchlorate

anions is also located on this threefold

axis. The calcium ion is octahedrally coordinated by glycyl car-

bonyls belonging to the

two

peptides, at an average distance of

2.26

A. The individual conformations ofthe two peptides form-

ing the sandwich (call them A and B) show considerable differ-

ences from each other (Table

3).

Their conformations are also

different from the

(PG)3 conformation

of the uncomplexed mol-

ecule described earlier as well as from the symmetric

3--y-turm

structure proposed (7) for uncomplexed (PG)3 in nonpolar sol-

Table

Torsion angles (in

degrees)

of the

(PO)3

molecule

Residue

no.

Residue

Pro

-56

153

.179

5 11 -23

25 --19

Gly

-125

-174

Pro

-78

-8 -170

-15 34 -41

31 -10

Gly

90 .159

Pro

-77 -10

170

-8 13 -15 -10

Gly

-96 -163 -178

4),

and w are the main-chain torsion angles (20).

Xo,

X2,

X3,

and

X4 are the

intraring

torsion

angles

of the

proline ring. They

denote the

angles about

N-CA, C]-CA', Ce-Ct C7-C¶

and

C5-N bonds,

respectively.

vents

(see

Fig. 4). However, the conformation of molecule A

is very similar to that proposed (7) for the 1:2 complexes of this

type, in which the prolyl carbonyls and the glycyl carbonyls

point to the opposite sides of the peptide ring. The sandwich

is also stabilized

by N-H'0Obonds between

the molecules B

and A. This sandwich type of cation entrapment is different from

the earlier observations

the crystal

structures

(5, 6, 21-23),

in which the cation is associated with a

single peptide. The pep-

tide-calcium sandwich has,

addition, swater

molecules on one

side and

a perchlorate anion on the other. The water molecules

are involved in O-H ..O hydrogen bonds with the prolyl

car-

bonyls of molecules A, resulting in-the formation of a-hydrogen-

bonded ring, while the perchlorate takes part

N-H--O

hy-

drogen bonds

with

glycyl

nitrogens of molecule

The

coun-

C104

-I^

jNd

FIG. 2. Calcium is sandwiched between the

two

peptide molecules

A and B and has six

coordinating glycyl carbonyl

oxygen

atoms

average

distance of

2.26-A.

There

are

interpeptide

N-IF

hydrogen

bonds stabilizing the sandwich. The sandwich is bound

perchlorate

anion

on one

side and

water

molecules forming

hydrogen-bonded

ring

with the

prolyl carbonyl

oxygens

the other side. The

complex

has

vertical threefold axis

passing through

the center of the

peptide

rings,

the calcium

atom, and the perchlorate.

4520

Chemistry:

Kartha

Conformationof 'Eyco(-L-Pro-Gly-)3 And Its Ca2' And Mg2 Complexes Page 2

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