Structure of an archaeal-type phosphoenolpyruvate carboxylase sensitive to inhibition by aspartate
Lakshmi Dharmarajan
Virginia Bioinformatics Institute, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Genetics, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Search for more papers by this authorJessica L. Kraszewski
Virginia Bioinformatics Institute, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Biological Sciences, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Search for more papers by this authorBiswarup Mukhopadhyay
Virginia Bioinformatics Institute, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Biological Sciences, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Department of Biochemistry, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Search for more papers by this authorCorresponding Author
Pete W. Dunten
Stanford Synchrotron Radiation Lightsource, Stanford University, Menlo Park, California 94025
Stanford Synchrotron Radiation Lightsource, Stanford University, Menlo Park, CA 94025===Search for more papers by this authorLakshmi Dharmarajan
Virginia Bioinformatics Institute, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Genetics, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Search for more papers by this authorJessica L. Kraszewski
Virginia Bioinformatics Institute, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Biological Sciences, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Search for more papers by this authorBiswarup Mukhopadhyay
Virginia Bioinformatics Institute, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Biological Sciences, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Department of Biochemistry, Bioinformatics and Computational Biology Graduate Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061
Search for more papers by this authorCorresponding Author
Pete W. Dunten
Stanford Synchrotron Radiation Lightsource, Stanford University, Menlo Park, California 94025
Stanford Synchrotron Radiation Lightsource, Stanford University, Menlo Park, CA 94025===Search for more papers by this authorAbstract
The crystal structure of an archaeal-type phosphoenolpyruvate carboxylase from Clostridium perfringens has been determined based on X-ray data extending to 3 Å. The asymmetric unit of the structure includes two tetramers (each a dimer-of-dimers) of the enzyme. The precipitant, malonate, employed for the crystallization is itself a weak inhibitor of phosphoenolpyruvate carboxylase and a malonate molecule is seen in the active-site in the crystal structure. The allosteric binding sites for aspartate (an inhibitor) and glucose-6-phosphate (an activator) observed in the Escherichia coli and Zea mays phosphoenolpyruvate carboxylase structures, respectively, are not conserved in the C. perfringens structure. Aspartate inhibits the C. perfringens enzyme competitively with respect to the substrate, Mg++. phosphoenolpyruvate. A mechanism for inhibition is proposed based on the structure and sequence comparisons with other archaeal-type phosphoenolpyruvate carboxylases with differing sensitivity to inhibition by aspartate. Proteins 2011; © 2011 Wiley-Liss, Inc.
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