Carbohydrates Special Issue

Carbohydrate Chemistry and Glycobiology: A Web Tour

Cover As the 23 March 2001 Special Issue of Science illustrates, the chemistry and biology of carbohydrates has evolved into a vast, many-sided discipline. To provide a bit of context, we've gathered together in the following paragraphs links to some particularly interesting Web resources in organic chemistry, carbohydrate chemistry and glycobiology.

Note: Before starting, the reader may want to consider downloading and installing the Chime plug-in from MDL Information Systems. Many of the more interesting chemistry and biochem sites on the Web, including most of the ones discussed here, rely heavily on Chime, which allows interactive 3D viewing of molecular structures, and lets the user rotate the molecules on-screen, zoom in and out, change display parameters, and perform many other transformations. The plug-in, which is available for both PC and Mac platforms running Internet Explorer 4/5 and Netscape 4.7, is free and takes about five minutes to download and install. (Those on Unix platforms or using older browser releases can get some of the same functionality with another helper program, Chime's widely used precursor, RasMol.)

General Organic Chemistry

Tutorials. Readers a bit rusty on their basic organic chemistry will find a number of excellent Web destinations for brushing up. The well-known MIT Biology Hypertextbook includes a straightforward chemistry review chapter (along with a nice page on sugars in large-molecules section). The Chemistry Department at the University of Akron offers a set of supplemental online slides and movies to the book General, Organic, and Biochemistry by James Hardy; among the offerings are chapters on carbohydrates and carbohydrate metabolism. And the handsomely designed CHEMystery site, a finalist in the 1996 ThinkQuest Internet Challenge, features a set of basic organic chemistry and biochem pages, pitched at the advanced high school level and including some very basic info on carbohydrates.

For users seeking something a bit fancier, the Chemistry Department of the University of Illinois at Chicago has assembled a JavaScript- and Chime-driven Organic Chemistry Online Tutorial at the undergraduate level, with nice reviews of bonding, functional groups, and stereochemistry. Michigan State University offers a full-featured Organic Chemistry Virtual Textbook that includes 3D renderings of selected molecules, also driven by the Chime plug-in. Colby College has built a set of Visual Aids for Organic Chemistry, consisting of a series of click-through slide shows (requiring the popular Shockwave plug-in from Macromedia). And Dr. R. Ehler of Germany has put together a set of interactive 3D renderings of Basic Reactions in Organic Chemistry; to view them, you'll need a Virtual Reality Markup Language (VRML) plug-in like CAI's Cosmoplayer.

A few other worthwhile sites for those seeking basic chemistry and organic chemistry info:

Nomenclature. The International Union of Pure and Applied Chemistry is probably the best first stop for coming to grips with the organic chemistry nomenclature. The IUPAC offers, among many other things, a Glossary of Class Names of Organic Compounds and Reactive Intermediates Based on Structure, as well as other glossaries in physical organic chemistry, bioinorganic chemistry, and medicinal chemistry. Also available is an online version of "The Gold Book," IUAPC's 1997 compendium of chemical terms.

The Brunel University Chemistry Department, meanwhile, offers up a somewhat more accessible list of common definitions and terms in organic chemistry. And Dave Woodcock, at the Okanagan University College Chemistry Department, has developed a very nice tutorial on organic nomenclature that places names, formulas, and line drawings side by side with 3D Chime visualizations of the molecules in question.

Visualizing molecules. Any of a number of Web archives will provide 3D views of biochemically important organic molecules. Best place to start: Klotho, a "Biochemical Compounds Declarative Database" at Washington University of St. Louis that includes 439 unique compounds of biochemical significance. Clicking on a link in the database's alphabetical list (such as this one for 6-deoxy-D-altrose) offers links to a Fischer diagram of the molecule, an interactive 3D view for users with the Chime plug-in installed, and a static 3D .gif image for users without Chime.

Even more impressive are the archives of 3D structures built around Chime. Flick Coleman of the Wellesley College Department of Chemistry has compiled a collection of hundreds of molecular structures in Chime, packaged within a convenient JavaScript-driven browser interface that lets the user easily perform some standard queries and transformations. At Okanagan University College, a collection of 1400 molecular models in PDB format (viewable using Chime or RasMol) has been created by Dave Woodcock. And a commercial site, WebMolecules, claims to have an astonishing 220,000 3D molecular models (including 35 carbohydrates) available for free viewing, accessible either using Chime or a VRML plug-in such as Cosmoplayer.

Stereochemistry and chirality. The principles of stereochemistry and the concepts of isomerism and chirality assume particular importance in carbohydrate science. Those unfamiliar with these concepts, or those merely needing a refresher, can turn to a straightforward chirality tutorial in the superb Interactive Biochemistry Website built to supplement the Garrett and Grisham print textbook.

At the Chiral Information Home Page, you can download a PDF-formatted review of stereochemistry and follow links to other chirality resources. One of those, Describing Chirality, provides an intuitive discussion of "handedness" in contexts far removed from chemistry. More specialized is the Online Guide to Chiral HPLC, geared specifically toward those interested in high-performance liquid chromatography but with much excellent general information on chirality.

Also highly recommended are the Colby College Organic Chemistry Virtual Tutor presentation on chirality and stereochemistry (requires Shockwave); the stereochemistry module of the University of Illinois' Organic Chemistry Online; and the Chime-based Introduction to Stereochemistry from Okanagan University College (embedded in the site's Basic Organic Nomenclature tutorial), which affords a good intuitive grasp of wedge diagrams, sawhorse diagrams, and Fischer projections by allowing the user to compare the 3D Chime renderings with the 2D projections.

Finally, the IUPAC's Basic Terminology of Stereochemistry provides a comprehensive source for looking up potentially unfamiliar stereochemical lingo.

Carbohydrate Nomenclature and Structure

Basic information on carbohydrates. Brief, one-page "what are carbohydrates" descriptions show up on wide variety of sites on the Web; nice examples can be found in the carbohydrate chemistry section of a New Zealand commercial site, Industrial Research Ltd., and in a set of pages for an introductory cell biology course at North Park University in Chicago. A more thorough introduction resides in the Medical Biochemistry pages of the Terre Haute Center for Medical Education (THCME). There, a lengthy entry on the biochemistry of carbohydrates (part of a larger section on the basic chemistry of biomolecules) walks the user in no-nonsense fashion through the essentials of carbohydrate nomenclature, classification, and structure. Also included on the site are good introductory write-ups on glycoproteins (in the context of a larger discussion on protein post-translational modifications), glycogen metabolism, and a wide variety of other topics in biochemistry and molecular biology. Highly recommended.

For those seeking something a bit more graphical, the Chemistry Department of the University of Kansas has posted a set of slides on carbohydrates that provides good basic information, as does the set of carbohydrate slides offered by the University of Akron.

Carbohydrate nomenclature. In addition to the other nomenclature and glossary resources already disussed under organic chemistry, the IUPAC offers up an exhaustive, well-documented set of guidelines on carbohydrate nomenclature that users will definitely want to bookmark as a reference.

Carbohydrate structure. 3D visualizations and animations of molecular structures constitute one of the Web's most potentially fruitful contributions to a basic understanding of carbohydrate chemistry. One place to start is New York University's Library of 3-D Molecular Structures, which includes ball-and-stick visualizations of six sugar molecules (available as static GIF images and also in more interactive VRML and Chime formats). In the U.K., biochemist/author Jon Maber has assembled a set of sugar-oriented WWW Resources for Biochemistry that includes a novel Java-based applet called the Monosaccharide Browser. The browser lets you choose among space-filling Fischer projections of 45 different monosachharides, either by selecting the molecule's name or by editing the structure directly; you can also alter chirality by clicking directly on the carbon atoms. Overall, the tool provides a nice feel for basic monosaccharide structure and terminology.

The best sites for visualizing carbohydrate structure, however, are those built around the Chime plug-in. If you've equipped your browser with this plug-in, head first to Sugar Molecules for Biochemistry, part of a larger set of molecular-structure images at Carnegie Mellon University called Building Blocks for Biochemistry. The page places interactive Chime images of monosaccharides and disaccharides side by side for comparison; a separate page on the site explores structures for modified sugars and oligosaccharides. Interactive Biochemistry offers up a set of carbohydrate Chime structures for viewing, rotating, and editing. And the University of Arizona Biochemistry Department has assembled some excellent models of monosaccharides and disaccharides, with explanatory glosses in the right-hand frame. (The site also includes some interesting material on glycoproteins, discussed below.)

Once you're used to manipulating the Chime images on screen, head to these other sites:

  • C4 Molecular Library at Cabrillo College, an NSF-funded archive of molecular structures. The site's MonoViewer lets you load up any of 30 separate carbohydrate structures in a well-designed, screen-filling window interface; with the DuoViewer, you can put two models on the screen for comparison.
  • Mol4D, a set of interactive organic chemistry tutorials at the University of Nijmegen's Centre for Molecular and Biomolecular Informatics. The site's glucose animations page lets you rotate a Chime structure of D-glucose to compare it with the Fischer projection, and view a Chime-based animation showing the transformation from the chainlike structure of D-glucose to the ring sugar beta-D-glucopyranose. (Excellent material on stereochemistry and other topics here as well.)
  • Oxford University's Molecule of the Month pages. A nice set of models of complex carbohydrates provides a look at cellobiose, maltose, lactose, and sucrose.

Finally, if you're in a less passive, more creative mood, check out Sweet 2, a Web-based program housed at the German Cancer Research Center's Central Spectroscopy Department. The program lets you build 3D models of saccharide structures on the fly by entering their sequences in an online form; you can then view the structures interactively using Chime or RasMol, a VRML viewer, or a Java applet, WebMol, that provides Chime-like functionality without the external plug-in. Very nicely done.

Glycobiology and Protein-Carbohydrate Interactions

Glycolysis. Information on the basics of sugar metabolism is quite plentiful on the Web; excellent first stops include the glycolysis page at the THMCE Medical Biochemistry site mentioned earlier in this review, and a series of slides on carbohydrate structure and metabolism archived in the Medical Biochemistry pages of the University of Kansas Medical Center.

For visualizing the actual pathways of glycolysis, start with Glycolysis: The Universal Energy Pathway, at the superb BioTech site at the University of Texas. Here you'll find straightforward descriptions of the main glycolysis reactions, and a graphical pathway linked to .gif images of the glycolysis intermediates and to Chime- or RasMol-viewable models of the key enzymes. Another site, Metabolic Pathways of Biochemistry (George Washington University), offers both a 2D and Chime-powered 3D chart of the glycolysis pathway. Other excellent Chime-based journeys through the glycolysis pathway include Images of Glycolysis Intermediates, a nicely designed summary at the Molecular Models for Biochemistry site of Carnegie Mellon University; and The Glycolytic Cycle, a handsome 3D chart of glycolysis intermediates and important enzymes (part of a larger site, Biochemistry Notebook, built by L. Van Warren).

Finally, to start exploring the interactions between proteins and carbohydrates a bit more thoroughly, have a look at the Enzymes of Glycolysis section of Chime Square, a part of the Biochemistry and Molecular Biology Online area maintained by Southern Illinois University. The well-designed and annotated Chime images archived here graphically show the binding of the sugar and enzyme molecules and the active site residues for various glycolytic catalysts from a variety of organisms.

Glycoproteins. As noted earlier, the THCME Medical Biochemistry pages include some good introductory information on glycoproteins, with discussions of N and O linkage and the clinical implications of protein-sugar interactions. The IUPAC offers a guide to the nomenclature of glycoproteins, glycopeptides, and peptidoglycans with a wealth of useful basic information that goes well beyond the limited ambit of nomenclature. Also worth a visit is a set of pages on the structure and biosynthesis of N-glycans, by Christian Frosch of the University of Mainz Institute of Toxicology.

The general field of protein-sugar interactions has spurred some particularly fine 3D visualizations using Chime. One of the best is Sugar & Co., which includes an especially instructive demo on the workings of the E. coli maltose binding protein. Another excellent tutorial, on maltoporin, can be found at the Online Macromolecular Museum of California Lutheran University. The University of Arizona Biochemistry Department offers a very nice 3D Chime image of an N-linked glycoprotein (as well as a rather hyperkinetic animated .gif image that purports to show carbohydrate mobility in a glycoprotein). And a set of Chime-based class projects for an upper-division course on molecular cell physiology at the University of Colorado, taught by Mark Dubin, includes fascinating material on cellobiohydrolase I, the Ebola virus glycoprotein, the glycolytic pathway, and the interaction of porin and sucrose.

A few other molecular-visualization resources worth exploring:

Databases. Here are some of the searchable databases on carbohydrate science and glycobiology that have emerged in the past several years.

Searchable archive of complex carbohydrate structure data.
A search on the keyword glycoprotein at the celebrated respository for protein-sequence information returned a list of nearly 9500 entries, each of them amply cross-linked to sequence, structural, and other data.
Carbohydrate-Active Enzymes (CAZy)
Manually curated, nonredundant collection covering nearly 200 families of enzymes dedicated to the degradation, synthesis, and modification of carbohydrates and of their ancilliary modules. Contains sequence and structural information on some 9000 proteins, including glycosidases and transglycosylases, glycosyltransferases, polysaccharide lyases, carbohydrate esterases, and carbohydrate-binding modules.
A database of 198 O-glycosylated proteins, run by the Center for Biological Sequence Analysis at the Technical University of Denmark.
Well-crafted, curated database of glycoprotein glycan structures compiled by the commercial firm Proteome Systems, Ltd., and freely available for use by nonprofit organizations.
A promising and, frankly, very cool gateway that seeks to gather a ton of glycomics information into a convenient, freely available hubsite. The one very big disadvantage: At present, the site works only with Internet Explorer.

Carbohydrate and Glycobiology
Societies and Portals

We close with a brief review of some interesting portal-like entries in carbohydrate chemistry and glycoscience -- convenient jumping-off points for further exploration.

ACS Carbohydrate Division
The American Chemical Society's carbohydrates area includes information on upcoming meetings, an archive of the division's newsletters, links to carbohydrate Websites, and tips on employment opportunities.
Complex Carbohydrate Research Center
NIH- and DOE-funded center doing research on custom carbohydrate synthesis, glycoconjugate molecules, and a variety of other areas.
The Glycoscience Network
An easy-to-use, well-maintained location with a fairly rich collection of carbohydrate and glycoscience links, as well as information about upcoming meetings and courses.
Society for Glycobiology
Online headquarters of the nonprofit professional organization that publishes the monthly journal Glycobiology.
Oxford Glycobiology Institute
Research institute studying glycoprotein and glycolipid biosynthesis, glycoimmunology, glycoproteomics, and structural glycobiology.
A very nice, still-evolving portal from Japan, with a rich collection of articles on glycoprotein, carbohydrate signalling, glycotechnology, glycopathology, and other topics.