Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.3.36 (naphthoate synthase)
 12 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menaquinone (MK) plays a central role in the respiratory chain of Bacillus subtilis. The biosynthesis of MK requires the formation of a naphthoquinone ring via a series of specific reactions branching from the shikimate pathway. "Early" MK-specific reactions catalyze the formation of o-succinylbenzoate (OSB) from isochorismate, and "late" reactions convert OSB to dihydroxynaphthoate, by utilizing an OSB-coenzyme A intermediate. We have cloned and sequenced the B. subtilis menE and menB genes encoding, respectively, OSB-coenzyme A synthase and dihydroxynaphthoate synthase. The MenB open reading frame encodes a potential polypeptide of 261 amino acid residues with a predicted size of 28.5 kDa, while the MenE open reading frame could encode a 24.4-kDa polypeptide of 220 amino acid residues. Probable promoter sequences were identified by high-resolution primer extension assays. Organization of these genes and regulatory regions was found to be menBp menB menEp menE. Expression of menE was dependent on both menEp and menBp, indicating an operonlike organization. A region of dyad symmetry capable of forming a stable RNA secondary structure was found between menB and menE. Culture cycle-dependent expression of menB and menE was measured by steady-state transcript accumulation. For both genes, maximal accumulation was found to occur within an hour after the end of exponential growth. The menBp and menEp promoters have sequences compatible with recognition by the major vegetative form of B. subtilis RNA polymerase, E sigma A. Both promoter regions also were found to contain homologies to a sequence motif previously identified in the menCDp region and in promoters for several B. subtilis tricarboxylic acid cycle genes.
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PMID:Sequence organization and regulation of the Bacillus subtilis menBE operon. 162 63

Menaquinone (vitamin K2)-deficient mutants of Bacillus subtilis, whose growth requirement is satisfied by 1,4-dihydroxy-2-naphthoic acid but not by o-succinylbenzoic acid (OSB), have been analyzed for enzymatic defects. Complementation analysis of cell-free extracts of the mutants revealed that there are two groups, as already indicated by genetic analysis. The missing enzyme in each group was identified by complementation of the cell-free extracts with o-succinylbenzoyl-coenzyme A (CoA) synthetase and dihydroxynaphthoate synthase extracted from Mycobacterium phlei. Mutants found to lack dihydroxynaphthoate synthase, and which therefore complement with dihydroxynaphthoate synthase of M. phlei, were designated as menB; those lacking o-succinylbenzoyl-CoA synthetase, and therefore complementing with o-succinylbenzoyl-CoA synthetase, were designated as menE. The menB mutants RB413 (men-325) and RB415 (men-329), when incubated with [2,3-14C2]OSB, produced only the spirodilactone form of OSB in a reaction that was CoA and adenosine 5'-triphosphate dependent.
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PMID:Identification of Bacillus subtilis men mutants which lack O-succinylbenzoyl-coenzyme A synthetase and dihydroxynaphthoate synthase. 678 May 15

Mycobacterium tuberculosis, the cause of tuberculosis, is one of the most devastating human pathogens. New drugs for its control are urgently needed. Menaquinone, also known as vitamin K, is an essential cofactor that is required for electron transfer and the enzymes that synthesize it are therefore potential drug targets. The enzyme naphthoate synthase (MenB) from M. tuberculosis has been expressed in Escherichia coli, purified and crystallized both as the native enzyme and in complex with naphthoyl-CoA. Both structures have been determined by X-ray crystallography: native MenB at 2.15 A resolution (R = 0.203, R(free) = 0.231) and its napthoyl-CoA complex at 2.30 A resolution (R = 0.197, R(free) = 0.225). The protein structure, which has a fold characteristic of the crotonase family of enzymes, is notable for the presence of several highly flexible regions around the active site. The bound naphthoyl-CoA is only visible for one of the three molecules in the asymmetric unit and only partly rigidifies the structure. The C-terminal region of the protein is seen to play a critical role both in completion of the binding pocket and in stabilization of the hexamer, suggesting a link between oligomerization and catalytic activity.
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PMID:Structure of naphthoate synthase (MenB) from Mycobacterium tuberculosis in both native and product-bound forms. 1613 52