PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Microbiome: Expanding the Gut Gene Catalog
November 2014
Complex Search
September 2014
Repairing a Rift
September 2014
iTRAQing the Ubiquitinome
July 2014
Immunity: Clustering Immunoglobulins
June 2014
Mining Protein Dynamics
May 2014
Design and Discovery: Identifying New Enzymes and Metabolic Pathways
January 2014
Epigenetics: Tracing Histone Demethylase Inhibitors
December 2013
Cancer Networks: Predicting Catalytic Residues from 3D Protein Structures
November 2013
Protein-Nucleic Acid Interaction: Inhibition Through Allostery
July 2013
Infectious Diseases: Targeting Meningitis
May 2013
Protein Interaction Networks: Reading Between the Lines
April 2013
Design and Discovery: A Cocktail for Proteins Without ID
February 2013
Targeting Enzyme Function with Structural Genomics
July 2012
More in one
June 2012
Disordered Proteins
February 2012
RNA Chaperone NMB1681
July 2011
Capsid assembly in motion
April 2011
One at a time
April 2011
A growing family
February 2011
Predicting functions within a superfamily
January 2011
Isoxanthopterin Deaminase
November 2010
Scaling up mutational scanning
November 2010
Alpha/Beta Barrels
October 2010
Mre11 Nuclease
May 2010
Assigning protein function: GeMMA
April 2010
Face off
October 2009

Technology Topics Annotation/Function

Alpha/Beta Barrels

SBKB [doi:10.3942/psi_sgkb/fm_2010_10]
Featured System - October 2010
Short description: How are these six proteins similar? They all perform very different functions: they represent five different classes of enzymes, and one is a non-enzymatic protein.

How are these six proteins similar? They all perform very different functions: they represent five different classes of enzymes, and one is a non-enzymatic protein. They all have very different oligomeric structures, ranging from monomeric to decameric assemblies. They all have very different chain lengths. However, in spite of these differences, they all have one central similarity: they all fold into a classic alpha/beta barrel.

Finding Folds

Researchers at PSI JCMM and PSI JCSG have been analyzing the genome of the bacterium Thermatoga maritima to discover similarities like this. Using information in the genome and known structures of proteins, they reconstructed a model of the central metabolic network of the bacterium, defining the proteins and small molecules that perform the major processes of life. The result is a network of 478 proteins (120 with known structures, and the rest modeled) and 503 small molecules, all interacting in 645 reactions.

Evolving Functions

Given this comprehensive information, we can now start asking interesting questions about the evolution of self-sustaining organisms. It has been known for some time that many proteins have similar folding patterns, and several hypotheses have been proposed to account for this. It could be that a stable protein fold (like the alpha/beta barrel) evolves once, and then diversifies through gene duplication to create many similar enzymes with different functions. Alternatively, proteins with many different folds can evolve separately to perform similar functions.

Network Analysis

The network analysis reveals, as is often the case with biology, the cells take all of these approaches. In this bacterium, about 11% of the proteins are examples of similar structures performing similar functions. However, many examples are also found of enzymes with similar function but very different structures. The six proteins shown here are examples of yet another relationship, where a particularly successful folding pattern (the alpha/beta barrel) is used in many different functions.

TIM Barrels

The alpha-beta barrel is the most common protein fold found in Thermatoga maritima. In these proteins, the chain forms a series of alternating alpha helices and beta sheets, which then wrap into a stable, cylindrical structure. This fold is often called a "TIM barrel" because there is a particularly symmetrical example in the enzyme triose phosphate isomerase (shown here from PDB entry 1tim). You can click on the TIM barrel image to get a Jmol of the six proteins from Thermatoga, all overlapped to show the similarities and differences between their folding patterns (PDB entries 1vkf, 1zy9, 1o0y, 1j5s, 1vrd and 1vpx).

The JSmol tab below displays an interactive JSmol

Nitrobindin (PDB entry 3emm)

This image includes one subunit of the nitrobindin dimer, the heme, and a water molecule (shown in turquiose) in the position where nitric oxide is thought to bind. The histidine that coordinates to the heme iron is also shown. Use the buttons below to change the representation. In the spacefilling representation, notice that the heme iron is exposed to the surrounding solvent. Using the backbone representation colored by secondary structure, find the short 310 helix that closes off t


  1. Zhang, Y. et al. Three-dimensional structural view of the central metabolic network of Thermatoga maritima. Science 325: 1544-1549 (2009).

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health