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1.
J Microbiol ; 52(6): 490-5, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24610334

ABSTRACT

Prephenate dehydratase is a key enzyme of the biosynthesis of L-phenylalanine in the organisms that utilize shikimate pathway. Since this enzymatic pathway does not exist in mammals, prephenate dehydratase can provide a new drug targets for antibiotics or herbicide. Prephenate dehydratase is an allosteric enzyme regulated by its end product. The enzyme composed of two domains, catalytic PDT domain located near the N-terminal and regulatory ACT domain located near the C-terminal. The allosteric enzyme is suggested to have two different conformations. When the regulatory molecule, phenylalanine, is not bound to its ACT domain, the catalytic site of PDT domain maintain open (active) state conformation as Sa-PDT structure. And the open state of its catalytic site become closed (allosterically inhibited) state if the regulatory molecule is bound to its ACT domain as Ct-PDT structure. However, the X-ray structure of prephenate dehydratase from Streptococcus mutans (Sm-PDT) shows that the catalytic site of Sm-PDT has closed state conformation without phenylalanine molecule bound to its regulatory site. The structure suggests a possibility that the binding of phenylalanine in its regulatory site may not be the only prerequisite for the closed state conformation of Sm-PDT.


Subject(s)
Prephenate Dehydratase/chemistry , Streptococcus mutans/enzymology , Crystallography, X-Ray/methods
2.
Int J Biol Macromol ; 49(4): 761-6, 2011 Nov 01.
Article in English | MEDLINE | ID: mdl-21798280

ABSTRACT

Prephenate dehydrogenase (PDH) is a bacterial enzyme that catalyzes conversion of prephenate to 4-hydroxyphenylpyruvate through the oxidative decarboxylation pathway for tyrosine biosynthesis. This enzymatic pathway exists in prokaryotes but is absent in mammals, indicating that it is a potential target for the development of new antibiotics. The crystal structure of PDH from Streptococcus mutans in a complex with NAD(+) shows that the enzyme exists as a homo-dimer, each monomer consisting of two domains, a modified nucleotide binding N-terminal domain and a helical prephenate C-terminal binding domain. The latter is the dimerization domain. A structural comparison of PDHs from mesophilic S. mutans and thermophilic Aquifex aeolicus showed differences in the long loop between ß6 and ß7, which may be a reason for the high K(m) values of PDH from Streptococcus mutans.


Subject(s)
Prephenate Dehydrogenase/chemistry , Streptococcus mutans/enzymology , Amino Acid Sequence , Anti-Bacterial Agents/pharmacology , Binding Sites , Crystallography, X-Ray , Cyclohexanecarboxylic Acids/chemistry , Cyclohexanecarboxylic Acids/metabolism , Cyclohexenes/chemistry , Cyclohexenes/metabolism , Molecular Sequence Data , NAD/chemistry , NAD/metabolism , Streptococcus mutans/drug effects
3.
FEBS Lett ; 565(1-3): 181-7, 2004 May 07.
Article in English | MEDLINE | ID: mdl-15135076

ABSTRACT

PRL-3, a novel class protein of prenylated tyrosine phosphatase, is important in cancer metastasis. Due to its high levels of expression in metastatic tumors, PRL-3 may constitute a useful marker for metastasis and might be a new therapeutic target. Here, we present the solution structure of the phosphatase domain of a human PRL-3 (residues 1-162) in phosphate-free state. The nuclear magnetic resonance (NMR) structure of PRL-3 is similar to that of other known phosphatases with minor differences in the secondary structure. But the conformation and flexibility of the loops comprising the active site differ significantly. When phosphate ions or sodium orthovanadate, which is a known inhibitor, are added to the apo PRL-3, the NMR signals from the residues in the active site appeared and could be assigned, indicating that the conformation of the residues has been stabilized.


Subject(s)
Immediate-Early Proteins/chemistry , Neoplasms/enzymology , Neoplasms/pathology , Protein Tyrosine Phosphatases/chemistry , Amino Acid Sequence , Binding Sites , Enzyme Inhibitors/pharmacology , Humans , Ions , Ligands , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Sequence Data , Neoplasm Metastasis , Neoplasm Proteins , Phosphates/chemistry , Protein Conformation , Protein Structure, Secondary , Protein Structure, Tertiary , Sequence Homology, Amino Acid , Tyrosine/chemistry , Vanadates/chemistry , Vanadates/pharmacology
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