Modelling transition state analogues and enzyme-inhibitor complexes of zinc-containing class II aldolases and metalloproteases

Ruf, Michael; Weis, K. H.; Brasack, Ingo; Vahrenkamp, Heinrich

doi:10.1016/s0020-1693(96)05236-x

Cited by 48 publications

(65 citation statements)

References 22 publications

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“…Thereby 2g resembles the large number of TpZn chelate complexes which are frequently discussed as models for enzyme-inhibitor complexes. [27,28] The coordination of the zinc ion can be described as reasonably close to trigonal-bipyramidal, with N8 and O4 on the axis forming the long Zn-X bonds. Additional rigidity in the structure comes from a hydrogen bond between the NH group of the pyrazole coligand and one carboxamide oxygen atom.…”

Section: Zinc Complexes Of L 3 and Lmentioning

confidence: 99%

New Polar Pyrazolylborate Ligands and Their Basic Zinc Complex Chemistry

et al. 2006

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By refinement of Trofimenko's procedures, four new tris(pyrazolyl)borate (Tp) ligands bearing pyridyl and carboxamide substituents at the 3-positions of the pyrazole rings, were obtained. Two of them were identified by structure determinations of their potassium salts. Their coordinative properties were explored by preparing Tp*Zn-X complexes, with X = Cl, Br, I, NO 3 , OAc, phenolate, thiophenolate and diorganophosphate, including the cationic complexes [Tp*Zn·L] + with L = methanol and pyrazole. From the spectra and structure determinations of these complexes it has become evident

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Section: Zinc Complexes Of L 3 and Lmentioning

confidence: 99%

New Polar Pyrazolylborate Ligands and Their Basic Zinc Complex Chemistry

et al. 2006

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“…They do, however, justify their formulation as transition state analogues by their structural flexibility: while the acetohydroxamate complex of Tp*Zn is close to square pyramidal (TBP′ index 0.3, see below), the ZINCOV complex of the same Tp*Zn unit is close to trigonal bipyramidal 18 (TBP′ index 0.9). Thereby they are reminders of the geometrical softness of transition states in general and those of coordination number 5 in particular.…”

Section: Frozen Enzymesmentioning

confidence: 99%

Transitions, Transition States, Transition State Analogues: Zinc Pyrazolylborate Chemistry Related to Zinc Enzymes

1999

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“…[87] Their values of (amount TBP') av are 0.88, 0.73, 0.47, and 0.26, respectively. As described before for Figure 11 they were projected twice, yielding a total of 8 reaction steps.…”

Section: Proposed Reaction Trajectorymentioning

confidence: 96%

“…In order to generate a less crowded view of the proposed reaction trajectory, four complexes [Tp'Zn(X)(Y)] were selected that represent approximately equidistant steps along Zn(2-hydroxamato-4-methylpentaoylalanylglycylamide)], [87] [50] and [Tp Cum,Me…”

Section: Proposed Reaction Trajectorymentioning

confidence: 99%

Evidence for a Trajectory of Hydrolytic Reactions brought about by [L3Zn−OH] Species

et al. 1999

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A kinetic study has been performed on the hydrolytic cleavage of various triorganophosphates PO-(OR) 2 (OR') by three pyrazolylborate ± zinc hydroxide complexes [Tp'Zn À OH] to form [Tp'Zn À OPO(OR) 2 ] and HOR'. The nature of the reactions (first order both in the zinc complex and the phosphate) and the strongly negative activation entropies (À 54 to À 126 J mol) indicate an intimate association of the ZnÀOH and PO functions in the rate-determining step. Some ester cleavages by [Tp'Zn À OH] show the same kinetic pattern and similar activation parameters. The observations are in accord with a four-center arrangement (ZnOPO or ZnOCO) in the activated complex, that is, the hybrid mechanism discussed for zinc enzyme as well as zinc complex catalyzed hydrolyses. A trajectory for reactions passing through this intermediate has been constructed with the Bürgi ± Dunitz structure correlation method, based on the geometries of 30 [Tp'Zn(X)(Y)] species with truly five-coordinate zinc centers. Its first step is the approach of the substrates oxygen atom to the tetrahedral L 3 ZnÀOH species along the axis of a trigonal bipyramid. In the resulting four-center intermediate with five-coordinate zinc a Berry pseudorotation describes the synchronous formation of the Zn À O-(substrate) and breaking of the ZnÀO-(OH) bonds. The concluding step in the coordination sphere of zinc is the expulsion of the former OH oxygen, now part of the substrate, again along the axis of a trigonal bipyramid. This mechanism, which is applicable to phosphate as well as to ester, amide, and carbon dioxide hydrolysis, is in accord with theoretical models of carbonic anhydrase action.

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Modelling transition state analogues and enzyme-inhibitor complexes of zinc-containing class II aldolases and metalloproteases

Cited by 48 publications

References 22 publications

New Polar Pyrazolylborate Ligands and Their Basic Zinc Complex Chemistry

New Polar Pyrazolylborate Ligands and Their Basic Zinc Complex Chemistry

Transitions, Transition States, Transition State Analogues: Zinc Pyrazolylborate Chemistry Related to Zinc Enzymes

Evidence for a Trajectory of Hydrolytic Reactions brought about by [L3Zn−OH] Species

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