Computer Assisted Modeling Contributions of Computational Approaches to Elucidating Macromolecular Structure and Function (1987) / Chapter Skim
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8 Structure and Function of Complex Carbohydrates
8 Structure and Function of Complex Carbohydrates
Pages 131-143
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From page 131... ...
Many other naturally occurring complex carbohydrates are covalently connected to other molecules, such as proteins or lipids, by glycosidic linkages of the sugar residues at their reducing ends to form glycoconjugates. BlOLOGICAI' FUNCTION Glycoproteins have many functions in higher organisms.
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From page 132... ...
In addition, certain glycosphingolipids of the ganglio~ide class have been found recently to inhibit the mitogenic response of cell growth factors by allosteric modulation of their cell surface receptors (Bremer et al., 1986~. Oncogenic transformation by viral infection or chemical mutagens usually leads to alterations in the cell surface pattern of glycosphingolipids such that certain types increase greatly in quantity.
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From page 133... ...
, which is synthesized in the nucleus from free sialic acid and CTP. The enzymes involved in glycoconjugate biosynthesis are glycosy~transferases that catalyze the transfer of sugar residues from the sugar nucleotides to the nonreducing end of a growing carbohydrate chain.
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From page 134... ...
While the polypeptide chain is being translated on a messenger RNA and concurrently passed through the endoplasm~c reticulum membrane into the coeternal space (lumen) , a single oligosaccharide is coordinately synthesized on a photo phorylated polyisoprenoid alcohol (dolicho!
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From page 135... ...
greatest at neutral pH, in contrast with lysosomal enzymes that have their greatest catalytic activity at an acid pH. In eukaryotic ceils, the high mannose oligosaccharide with five mannose units (see Figure 8-1)
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From page 136... ...
Lysosomal enzymes contain one or more phosphate groups on mannose residues of the high mannose type oligosaccharide chains. The mannose-~phosphate groups are specific recognition markers that are involved in the transport of lysosomal enzymes from the Golgi apparatus or outside the cells into lysosomes.
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From page 137... ...
Three-dimensional structures of carbohydrates represent the spatial arrangements of the individual sugar residues. Most commonly occurring mammalian complex carbohydrates consist of sugar residues that exist in the pyranose ring form, the most stable and rigid conformation of which are the chair forms.
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From page 138... ...
is that conformer where the C-1 H-1 bond eclipses O-C'-X' and C-1-O eclipses C'-X' H-X'. The relative orientations of adjacent sugar residues in an oligosaccharide chain are described by specifying the rotational angles (¢, '6)
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From page 139... ...
This approach was subsequently extended by adapting energy calculations originally used for peptides, where the potential energy is divided into functions that describe Excrete contributions such as van der Waals energies, electrostatic interactions, torsional energy, hydrogen bond energy, and bond and angle deformations (Bock, 1983~. The data are presented In the form of computer-generated energy contour maps.
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From page 140... ...
yields energy minimization results that differ from those calculated by the HSEA method, from which geometries can be derived that differ from those obtained by the HSEA method. NMR SOLUTION STRUCTURES OF CARBOHYDRATES Proton NMR methods provide detailed experimental data from which three-dimensional structures can be determined and compared with conformations arrived at by potential energy calculations.
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From page 141... ...
Thus, it may be possible to determine solution conformations of the complex carbohydrates, even in nonrigid cases, using a combination of calculations and constraints imposed from experimental NMR data. Despite the questions raised about the interpretation of NMR results and the value of potential energy m~nirn~zations, some important information has been collected about interactions of carbohydrate antigens with antibodies (Lemieux et al., 1985)
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From page 142... ...
Surfaces that consist of more than one macromolecule often behave as a functional unit. For example, the uptake of cholesterol by many ceils requires the interaction of a specific cell surface receptor with a polypeptide surface of a complex supramolecular structure called low density lipoprotein (LJDL)
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From page 143... ...
A similar situation involving a lipid membrane Is found with a m~tochondrial enzyme, beta-hydroxybutyric dehydrogenase, which is catalytically active only when incorporated into a lipid bilayer composed of certain phospholipids. Computer-assisted mathematical modeling of such supramolecular structures will be necessary to gain a deeper understanding of the organization of biological materials for complex functions.
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