Purdue News
Purdue News
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March 2001 Scientists find great-granddaddy of enzyme familyWEST LAFAYETTE, Ind. – Scientists have traced a protein to the point in early evolution when it first began using a chemical, ATP, to power cells. ATP, or adenosine triphosphate, powers the machinery of cells by releasing energy when its phosphate chemical bond is broken. A study of the structure of an acetate kinase, an enzyme used in converting organic matter to methane, indicates that the enzyme may be the primordial, or earliest, protein to use ATP, say scientists at Purdue and Pennsylvania State universities. "The structure, plus biochemical considerations about the early evolution of life, suggest we may be getting a snapshot of what a protein from the very origin of protein-based life looks like," says David Sanders, assistant professor of biological sciences at Purdue, who directed the study. "Acetate is very easily synthesized under early earth conditions from things like carbon monoxide and methane, which were present in high concentrations in early life." The study, published in the Jan. 19 issue of the Journal of Bacteriology, provides science with a more complete picture of how proteins evolved and paints an image of very early cooperation between bacteria. Understanding the structure also may someday lead to the ability to control the enzyme, Sanders says, noting that acetate kinase comes from a methane-producing bacterium and is responsible for one-third of the global methane, a greenhouse gas. The structure also suggests that acetate kinase may be the common ancestor in a "superfamily" of enzymes known as phosphotransferases, named for their ability to make or break phosphate bonds in cells. This process, called phosphorylation, is used to initiate a number of activities, including cell movement, muscle movement and the metabolization of glucose. The research was a collaborative effort among Sanders; Miriam Hasson, assistant professor of biological sciences at Purdue; and James G. Ferry, professor of biochemistry and molecular biology at Penn State, known for his pioneering studies of methane production by bacteria. Acetate kinase is found in microbes of the bacteria and archaea domains. It plays a role in communication between different types of bacteria and performs a dual role in converting organic matter to methane. "In the process of decomposing organic matter to methane, acetate kinase is used in different ways by different bacteria," Sanders says. "While some bacteria use it as the last energy-generating step in the breakdown of complex molecules, other bacteria use the acetate kinase to create new metabolites." This cooperative process, with one organism carrying out part of the metabolism and a second organism doing another part, illustrates how early bacteria may have evolved together to undertake complex tasks. "This particular protein is an excellent model of very early cooperation between bacteria," Sanders says. "And that cooperation continues through this very day." The determination of the structure of acetate kinase confirms the earlier prediction by Sanders and Hasson that the structure of acetate kinase would closely resemble those of other enzymes such as actin, used for muscle movement, and hexokinase, which is used to metabolize glucose. The hypothesis was unusual because there was no similarity in the amino-acid sequences of acetate kinase and the other proteins. The researchers found that acetate kinase contains a core fold or shape that is identical to that found in hexokinase, actin and several other proteins in the enzyme superfamily. This similarity indicates these proteins shared a common ancestor during evolution. A number of facts point to the idea that it may have closely resembled the current acetate kinase. "Structural, biochemical and geochemical considerations indicate that an acetate kinase may be the ancestral enzyme of this superfamily of proteins," Sanders says. "This family probably originally evolved to perform one type of task and then advanced to perform other tasks." The divergent sequences found among the enzymes also suggest the superfamily dates back to an early time in evolution. "It takes time for sequences to evolve and diverge – and the more divergent they are, the more likely that the proteins are an ancient family," Sanders says. Source: David Sanders, (765) 494-6453, retrovir@bragg.bio.purdue.edu Writer: Susan Gaidos, (765) 494-2081; sgaidos@purdue.edu Purdue News Service: (765) 494-2096; purduenews@purdue.edu ABSTRACT Urkinase: The Structure of Acetate Kinase, a Member of the ASKHA Superfamily of Phosphotransferases Kathryn A. Buss, David R. Cooper, Cheryl Ingram-Smith, James G. Ferry, David Avram Sanders, Miriam S. Hasson Acetate kinase, an enzyme widely distributed in the Bacteria and Archaea domains, catalyzes the phosphorylation of acetate. We have determined the three-dimensional structure of Methanasarcina thermophila acetate kinase bound to ADP through crystallography. As we previously predicted, acetate kinase contains a core fold that is topologically identical to that of the ADP-binding domains of glycerol kinase, hexokinase, the 70-kD heat shock cognate and actin. Numerous charged active-site residues are conserved within acetate kinases, but few are conserved within the phosphotransferase superfamily. The identify of the points of insertion of polypeptide segments into the core fold of the superfamily members indicates that the insertions existed in the common ancestor of the phosphotransferases. Another remarkable shared feature is the unusual, epsilon conformation of the residue that directly precedes a conserved glycine residue (gly-331 in acetate kinase) that binds the alpha-phosphate of ADP. Structural, biochemical and geochemical considerations indicate that an acetate kinase may be the ancestral enzyme of the ASKHA (Acetate and Sugar Kinases/Hsc70/Actin) superfamily of phosphotransferases.
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