Coenzyme Interactions

Mieyal, John J.; Bantle, Gretchen; Votaw, Robert G.; Rosner, Itzhak; Sable, Henry Z.

doi:10.1016/s0021-9258(18)61896-4

Cited by 43 publications

(21 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In these structures there are basically two conformations that have been observed which are designated as the S and F forms.1 Ib The S form is characteristic of the thiamin when it is substituted at C(2) and is consistent with the interpretation of the NMR spectra of these compounds. 35,36,50 When thiamin is free of substituents on C(2), it has been found in the F form in over a dozen cases but only once in the S conformation. 34 None have yet been found in any other conformation including the proposed V form.2,9,12,51…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ring stacking interactions between thiamin and planar molecules as seen in the crystal structure of a thiamin picrolonate dihydrate complex

Shin¹,

Pletcher²,

Blank³

et al. 1977

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

“…42( 1) 51 (1) 50(1) 18(1) 16( 1) 21 (1) C(5P) 5838 motion. However, it is of interest that these values fall between the even shorter C(2')-C(2'o:) in thiamin pyrophosphate25 and Mg thiamin26 where there are close contacts with neighboring electronegative atoms and the longer bond in TCM22 where the methyl group is not in a polar environment.…”

Section: Methodsmentioning

confidence: 99%

Ring stacking interactions between thiamin and planar molecules as seen in the crystal structure of a thiamin picrolonate dihydrate complex

Shin¹,

Pletcher²,

Blank³

et al. 1977

J. Am. Chem. Soc.

View full text Add to dashboard Cite

“…At this point, the Hughes26 weighting scheme was replaced. The variance of F0 in the weighting scheme finally adopted is given by the expression, 07) 863 (2) 7620 (4) 2892 ( 5) 66 (2) 203 (5) 264 (8) 14( 2) 12(3) 43 (5) C( 8) 1953 (3) 4185 (3) 4624 ( 5) 138 (3) 118 (3) 301 (9)…”

Section: Methodsmentioning

confidence: 99%

Stereochemistry of intermediates in thiamine catalysis. I. Crystal structures of 2-(.alpha.-hydroxyethyl)-3,4-dimethylthiazolium bromide and DL-2-(.alpha.-hydroxyethyl)thiamine chloride hydrochloride

Sax¹,

Pulsinelli²,

Pletcher³

1974

J. Am. Chem. Soc.

View full text Add to dashboard Cite

The 2-(a-hydroxyethyl)-3,4-dimethylthiazolium ion is one of several models for 2-(a-hydroxyethyl)thiamine that were used in elucidating the mechanism of thiamine catalysis. The crystal structures of the title compounds were determined from X-ray diffraction data in order to (1) identify the characteristic steric features of the 2-(a-hydroxyethyl)thiazolium moiety and (2) examine the influence exerted on the thiamine structure when substituents of active intermediates are present at the C(2) position. Both structures were determined from diffractometer data using the 8-28 scan technique with Cu Ka radiation. The structures were refined by the fullmatrix least-squares method. The model compound crystalli5es in the monoclinic space group, P21/c, with unit cell parameters a = 9.771 ( 4 ) , b = 11.656 (3), c = 8.764 (2) A, p = 90.77 (4)O, and 2 = 4. The refinement of this structure converged to a conventional R factor of 0.049 over the 1439 independent observed reflections. The 2-(a-hydroxyethyl)thiamine chloride hydrochloride crystalgzes in the triclinic space group, PT, with unit cell parameters a = 12.811 (3), b = 10.749 (3), c = 7.108 (7) A, a = 108.43 (7), p = 99.05 (7), y = 96.02 (7)O, and 2 = 2. The refinement converged to a conventional R factor of 0.045 based on the 2823 observed reflections. A simple valence bond description of the resonance in the planar thiazolium ring is given which is consistent with the endocyclic bond lengths in both structures. It indicates that there is a partial positiye charge of = on the S atom. The observed intramolecular S . . .O interaction in both compounds, which is 0.4 A less than the normal van der Waals separation, provides evidence that the S bonds electrostatically with the unshared electrons on 0. The conformation of the 2-(a-hydroxyethyl) side chain appears to be strongly infiuenced by the S . e .O interaction. It is remarkably similar in the two compounds. The 0(2a)-C(2a)-C(2)-S(l) torsion angles agree to within 2.2O. The H(2)-0(2a>-C(2a)-C(2) torsion angles both deviate from 90' by less than 12' with the result that they both form a hydrogen bond which is nearly perpendicular to the plane of the thiazolium ring. The analysis of the thiamine derivative shows in addition that its conformation differs considerably from that of thiamine particularly with respect to the relative orientation of the pyrimidine and thiazolium rings. These conformational differences explain the reported shifts in the nmr spectra for these compounds in aqueous solution. On the basis of structural and spectral data, the thiamine and the 2-(a-hydroxyethyl)thiamine molecules may reasonably be expected to assume preferred conformations in aqueous solution closely resembling those in the solid state.uestions concerning details in the three-dimensional Q structure of 2-(a-hydroxyethyl)thiamine (1) have been raised in several papers dealing with the mechanism of thiamine c a t a l y s i~.~-~ In particular, the discussions on possible mechanistic roles for the 4'amino group have lead directly to specu...

show abstract

“…Sable and co-workers showed that hydroxyethylthiamin undergoes base-catalyzed proton exchange at the C-2a position and thus provided the first direct evidence for the existence of the free conjugate base. 13,14 The rate of the proton exchange reaction is very slow (half-life 5 h at pD 8.5, 50 °C, k = 4 X 10~4 S~'). This is consistent with the intermediate being a high-energy species due its very high basicity (estimated pK = 1715).…”

Section: Discussionmentioning

confidence: 99%

Chiral intermediates in thiamin catalysis. Stereochemical course of the decarboxylation step in the conversion of pyruvate to acetaldehyde

Kluger¹,

Karimian²,

Kitamura³

1987

J. Am. Chem. Soc.

View full text Add to dashboard Cite

The stereochemical course of the nonenzymic decarboxylation of the adduct of pyruvate and thiamin was determined. Racemic ethyl 2-(lact-2-yl)thiamin was resolved as the 2,3-dibenzoyltartrate salt under slightly acidic conditions. The specific rotations of the free enantiomers of ethyl 2-(lact-2-yl)thiamin are +8.4 f 0.1' and -8.4 f 0.1'. These were converted to the parent acid, 2-(lact-2-yl)thiamin, by acid hydrolysis. The (+) ethyl ester gave the (-) acid ( [ a ] 2 5 D -4.7 f 0.1") while the (-) ethyl ester gave the (+) acid ([a]25D = +4.7 f 0.1'). The acids were allowed to undergo spontaneous decarboxylation under a variety of conditions: aqueous solution, ethanol solution, dimethylformamide solution, and dimethylformamide solution containing brucine. Under all conditions the product was racemic 2 4 I-hydroxyethy1)thiamin. These results require that the reaction proceed via an achiral intermediate or rapidly equilibrating achirally solvated enantiomeric intermediates. Since it is known that enzymic reactions produce a single enantiomer of 2 4 1-hydroxyethyl)thiamin, the stereospecificity of the enzymic reaction is due to the chirality of the protein and not the intrinsic mechanism of the decarboxylation reaction. ( 5 ) Ullrich, J.; Mannschreck, A. Eur. J . Biochem. 1967, 1 , 110. (6) Kiuger, R.; Karimian, K.; Gish, G.; Pangborn, W. A,; DeTitta, G. T. J. Am. Chem. SOC. 1987, 109, 618. The title and caption to Figure 1 contain a typographical error. The enantiomer of HETI shown has a negatiue (but very weak) specific rotation (circular dichroism is preferred for the assignment), as stated in the rest of the paper. This material results from (+)hydroxyethylthiamin and the configuration at the stereocenter is R as indicated. We thank Professor W. Shin for noting the error.

show abstract

Coenzyme Interactions

Cited by 43 publications

References 15 publications

Ring stacking interactions between thiamin and planar molecules as seen in the crystal structure of a thiamin picrolonate dihydrate complex

Ring stacking interactions between thiamin and planar molecules as seen in the crystal structure of a thiamin picrolonate dihydrate complex

Stereochemistry of intermediates in thiamine catalysis. I. Crystal structures of 2-(.alpha.-hydroxyethyl)-3,4-dimethylthiazolium bromide and DL-2-(.alpha.-hydroxyethyl)thiamine chloride hydrochloride

Chiral intermediates in thiamin catalysis. Stereochemical course of the decarboxylation step in the conversion of pyruvate to acetaldehyde

Contact Info

Product

Resources

About