Structure of a triclinic ternary complex of horse liver alcohol dehydrogenase at 2.9 Å resolution

Eklund, Hans; Samma, J.P; Wallen, Leif; Brändén, Carl‐Ivar; Åkeson, Åke; Jones, Thomas A.

doi:10.1016/0022-2836(81)90047-4

Cited by 377 publications

(280 citation statements)

References 29 publications

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“…Alcohol dehydrogenase is known to assume two different main conformations, an open and a closed one [1][2][3] . The present calculations are based on a crystal structure of the closed conformation.…”

Section: The Relative Stability Of Four-and Five-coordinate Zinc Compmentioning

confidence: 99%

“…Yet, all experimental evidence (crystallographic and spectroscopic) agrees on that the free enzyme in the open conformation is four-coordinate [2][3]10,16,[19][20][21][22]44 . Further, it is widely assumed that the dehydration of the active site that occurs when the enzyme closes is important for the catalytic mechanism 1,2 .…”

Section: The Relative Stability Of Four-and Five-coordinate Zinc Compmentioning

confidence: 99%

“…The active site of the enzyme contains a zinc ion that is essential for catalysis. Crystallographic studies of the horse liver enzyme and its binary or ternary complexes with coenzyme and different substrates have shown that this zinc ion is bound to the enzyme through two cysteine and one histidine residue and that it, as a rule, is tetrahedrally four-coordinate with one water or substrate molecule (or the corresponding anions, depending on pH) as the fourth first-sphere ligand [2][3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

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Molecular dynamics simulations of alcohol dehydrogenase with a four‐ or five‐coordinate catalytic zinc ion

1995

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A detailed parameterization is presented of a zinc ion with one histidine and two cysteinate ligands, together with one or two water, hydroxide, aldehyde, alcohol, or alkoxide ligands. The parameterization is tailored for the active site of alcohol dehydrogenase and is obtained entirely from quantum chemical computations. The force‐field reproduces excellently the geometry of quantum chemically optimized zinc complexes as well as the crystallographic geometry of the active site of alcohol dehydrogenase and small organic structures. The parameterization is used in molecular dynamics simulations and molecular mechanical energy minimizations of alcohol dehydrogenase with a four‐ or five‐coordinate catalytic zinc ion. The active‐site zinc ion seems to prefer four‐coordination over five‐coordination by at least 36 kJ/mol. The only stable binding site of a fifth ligand at the active‐site zinc ion is opposite to the normal substrate site, in a narrow cavity behind the zinc ion. Only molecules of the size of water or smaller may occupy this site. There are large fluctuations in the geometry of the zinc coordination sphere. A four‐coordinate water molecule alternates frequently (every 7 ps) between the substrate site and the fifth binding site and even two five coordinate water molecules may interchange ligation sites without prior dissociation. Ligand exchange at the zinc ion probably proceeds by a dissociative mechanism. The results show that it is essential to allow for bond stretching degrees of freedom in molecular dynamics simulations to get a correct description of the dynamics of the metal coordination sphere; bond length constraints may restrict the accessible part of the phase space and therefore lead to qualitatively erroneous results. © 1995 Wiley‐Liss, Inc.

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Section: The Relative Stability Of Four-and Five-coordinate Zinc Compmentioning

confidence: 99%

Section: The Relative Stability Of Four-and Five-coordinate Zinc Compmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular dynamics simulations of alcohol dehydrogenase with a four‐ or five‐coordinate catalytic zinc ion

1995

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“…putida (pWW0) may be smaller than that in horse-liver alcohol dehydrogenase. In the horse-liver enzyme 13 amino acid residues line what is apparently a deep and hydrophobic cleft [24]. This substrate-binding cleft is found within individual subunits of the enzyme [24].…”

Section: Cleft Structure Active-site Structure and Substrate Specifimentioning

confidence: 99%

“…These are Cys-46, Asp-49, His-67, Glu-68, Val-80 and glycine residues 66, 71, 77, 86, 201, 204 and 235. There have not been any proposed catalytic roles for Val-80 and the conserved glycine residues, but they all have structural roles, some of which involve coenzyme binding [23][24][25][26]. Val-80, along with three of the conserved glycine residues (66, 71 and 77), His-67 and Glu-68, constitutes the characteristic zinc-dependent alcohol dehydrogenase motif GHEXXGXXXXXGXXV [27].…”

Section: Figure 2 Comparison Of a Segment Of The Primary Sequence Of mentioning

confidence: 99%

Molecular characterization of benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase II of Acinetobacter calcoaceticus

Gillooly

Robertson

Fewson

1998

Biochemical Journal

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The nucleotide sequences of xylB and xylC from Acinetobacter calcoaceticus, the genes encoding benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase II, were determined. The complete nucleotide sequence indicates that these two genes form part of an operon and this was supported by heterologous expression and physiological studies. Benzaldehyde dehydrogenase II is a 51654 Da protein with 484 amino acids per subunit and it is typical of other prokaryotic and eukaryotic aldehyde dehydrogenases. Benzyl alcohol dehydrogenase has a subunit Mr of 38923 consisting of 370 amino acids, it stereospecifically transfers the proR hydride of NADH, and it is a member of the family of zinc-dependent long-chain alcohol dehydrogenases. The enzyme appears to be more similar to animal and higher-plant alcohol dehydrogenases than it is to most other microbial alcohol dehydrogenases. Residue His-51 of zinc-dependent alcohol dehydrogenases is thought to be necessary as a general base for catalysis in this category of alcohol dehydrogenases. However, this residue was found to be replaced in benzyl alcohol dehydrogenase from A. calcoaceticus by an isoleucine, and the introduction of a histidine residue in this position did not alter the kinetic coefficients, pH optimum or substrate specificity of the enzyme. Other workers have shown that His-51 is also absent from the TOL-plasmid-encoded benzyl alcohol dehydrogenase of Pseudomonas putida and so these two closely related enzymes presumably have a catalytic mechanism that differs from that of the archetypal zinc-dependent alcohol dehydrogenases.

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Structural trees for protein superfamilies

Ефимов

1997

Proteins

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Structural trees for large protein superfamilies, such as beta proteins with the aligned beta sheet packing, beta proteins with the orthogonal packing of alpha helices, two-layer and three-layer alpha/beta proteins, have been constructed. The structural motifs having unique overall folds and a unique handedness are taken as root structures of the trees. The larger protein structures of each superfamily are obtained by a stepwise addition of alpha helices and/or beta strands to the corresponding root motif, taking into account a restricted set of rules inferred from known principles of the protein structure. Among these rules, prohibition of crossing connections, attention to handedness and compactness, and a requirement for alpha helices to be packed in alpha-helical layers and beta strands in beta layers are the most important. Proteins and domains whose structures can be obtained by stepwise addition of alpha helices and/or beta strands to the same root motif can be grouped into one structural class or a superfamily. Proteins and domains found within branches of a structural tree can be grouped into subclasses or subfamilies. Levels of structural similarity between different proteins can easily be observed by visual inspection. Within one branch, protein structures having a higher position in the tree include the structures located lower. Proteins and domains of different branches have the structure located in the branching point as the common fold.

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Structure of a triclinic ternary complex of horse liver alcohol dehydrogenase at 2.9 Å resolution

Cited by 377 publications

References 29 publications

Molecular dynamics simulations of alcohol dehydrogenase with a four‐ or five‐coordinate catalytic zinc ion

Molecular dynamics simulations of alcohol dehydrogenase with a four‐ or five‐coordinate catalytic zinc ion

Molecular characterization of benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase II of Acinetobacter calcoaceticus

Structural trees for protein superfamilies

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