Simultaneous inhibition of guinea pig brain 2′, 3′-cyclic nucleotide 3′-phosphohydrolase and myelin protein synthesis by 2′-adenosine monophosphate

Starich, Gale Hansen; Dreiling, Charles E.

doi:10.1016/0024-3205(80)90305-7

Cited by 11 publications

(2 citation statements)

References 16 publications

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“…To determine whether DTNB modification is active sitedirected, the ability of 2Ј-AMP, a product inhibitor (45,46), to protect against DTNB inactivation was tested. A high concentration of 2Ј-AMP was used to obtain maximum occupancy of the active site, since DTNB also acts as a reversible and competitive inhibitor with a K I value similar to that of 2Ј-AMP (K I ϭ 500 M).…”

Section: Resultsmentioning

confidence: 99%

Identification of Essential Residues in 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase

Lee¹,

Gravel²,

Gao

et al. 2001

Journal of Biological Chemistry

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2,3-Cyclic nucleotide 3-phosphodiesterase (CNP; EC 3.1.4.37) catalyzes in vitro hydrolysis of 3-phosphodiester bonds in 2,3-cyclic nucleotides to produce 2-nucleotides exclusively. N-terminal deletion mapping of the C-terminal two-thirds of recombinant rat CNP1 identified a region that possesses the catalytic domain, with further truncations abolishing activity. Proteolysis and kinetic analysis indicated that this domain forms a compact globular structure and contains all of the catalytically essential features. Subsequently, this catalytic fragment of CNP1 (CNP-CF) was used for chemical modification studies to identify amino acid residues essential for activity. 5,5-Dithiobis-(2-nitrobenzoic acid) modification studies and kinetic analysis of cysteine CNP-CF mutants revealed the nonessential role of cysteines for enzymatic activity. On the other hand, modification studies with diethyl pyrocarbonate indicated that two histidines are essential for CNPase activity. Consequently, the only two conserved histidines, His-230 and His-309, were mutated to phenylalanine and leucine. All four histidine mutants had k cat values 1000-fold lower than wild-type CNP-CF, but K m values were similar. Circular dichroism studies demonstrated that the low catalytic activities of the histidine mutants were not due to gross changes in secondary structure. Taken together, these results demonstrate that both histidines assume critical roles for catalysis.

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Section: Resultsmentioning

confidence: 99%

Identification of Essential Residues in 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase

Lee¹,

Gravel²,

Gao

et al. 2001

Journal of Biological Chemistry

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“…Although the function of CNPase remains an enigma, several speculations regarding its function have been put forward (see also Sims and Carnegie, 1978). CNPase has been implicated in the metabolism of myelin proteins (Stanch and Dreiling, 1980). By using 2'-AMP to inhibit CNPase competitively, the effect of decreased enzymic activity on the in vitro incorporation of ['4C]leucine into brain myelin protein synthesis was examined.…”

Section: Hypotheses Regarding the Function Of Cnpasementioning

confidence: 99%

Molecular Structure, Localization, and Possible Functions of the Myelin‐Associated Enzyme 2′,3′‐Cyclic Nucleotide 3′‐Phosphodiesterase

Vogel

Thompson

1988

Journal of Neurochemistry

144

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Triton X-100 extractions of central nervous system myelin indicate a possible role for the minor myelin proteins in the stability of lamellae

1988

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Isolated CNS myelin membranes were extracted with Triton X-100 under conditions previously established for the isolation of cytoskeletal proteins. Treated myelin retained much of its characteristic lamellar structure despite the removal of most of the major myelin basic protein (18.5 kDa) and the proteolipid protein, which together normally constitute 60% of the total myelin protein. The SDS-PAGE profile of this extract residue demonstrated an enrichment in proteins of Mr 30 to 60 kilodaltons (the Wolfgram group). The major myelin proteins were identified by antibodies on Western immunoblots, as were the 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNP), actin, tubulin, myelin-associated glycoprotein (MGP) and the 21.5 kDA MBP. The overall behavior of CNP, the 21.5 kDa MBP, MGP and tubulin towards Triton extraction is reminiscent of the behavior of other membrane-skeletal complexes, supporting the idea that these and other minor myelin proteins might be part of heteromolecular complexes with interactions spanning several lamellae of the myelin sheath.

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Simultaneous inhibition of guinea pig brain 2′, 3′-cyclic nucleotide 3′-phosphohydrolase and myelin protein synthesis by 2′-adenosine monophosphate

Cited by 11 publications

References 16 publications

Identification of Essential Residues in 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase

Identification of Essential Residues in 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase

Molecular Structure, Localization, and Possible Functions of the Myelin‐Associated Enzyme 2′,3′‐Cyclic Nucleotide 3′‐Phosphodiesterase

Triton X-100 extractions of central nervous system myelin indicate a possible role for the minor myelin proteins in the stability of lamellae

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