PDBsum entry 1adf

Oxidoreductase(NAD(a)-choh(d))

PDB id: 1adf

Contents

Protein chain

374 a.a.

Ligands

TAD

Metals

_ZN ×2

Waters ×102

References listed in PDB file

Key reference

Title

Crystallographic studies of two alcohol dehydrogenase-Bound analogues of thiazole-4-Carboxamide adenine dinucleotide (tad), The active anabolite of the antitumor agent tiazofurin.

Authors

H.Li, W.H.Hallows, J.S.Punzi, V.E.Marquez, H.L.Carrell, K.W.Pankiewicz, K.A.Watanabe, B.M.Goldstein.

Ref.

Biochemistry, 1994, 33, 23-32. [DOI no: 10.1021/bi00167a004]

PubMed id

8286346

Abstract

Thiazole-4-carboxamide adenine dinucleotide (TAD) is the active anabolite of the antitumor drug tiazofurin. Beta-methylene TAD (beta-TAD) is a phosphodiesterase-resistant analogue of TAD, active in tiazofurin-resistant cells. Beta-methylene SAD (beta-SAD) is the active selenium derivative of beta-TAD. Both agents are analogues of the cofactor NAD and are capable of acting as general dehydrogenase inhibitors. Crystal structures of beta-TAD and beta-SAD bound to horse liver alcohol dehydrogenase (LADH) are presented at 2.9 and 2.7 A, respectively. Both complexes crystallize in the orthorhombic space group C222(1) and are isomorphous to apo-LADH. Complexes containing beta-TAD and beta-SAD were refined to crystallographic R values of 15% and 16%, respectively, for reflections between 8 A and the minimum d spacing. Conformations of both inhibitors are similar. beta-TAD and beta-SAD bind to the "open" form of LADH in the normal cofactor-binding cleft between the coenzyme and catalytic domains of each monomer. Binding at the adenosine end of each inhibitor resembles that of NAD. However, the positions of the thiazole and selenazole heterocycles are displaced away from the catalytic Zn cation by approximately 4 A. Close intramolecular S-O and Se-O contacts observed in the parent nucleoside analogues are maintained in both LADH-bound beta-TAD and beta-SAD, respectively. These conformational constraints may influence the binding specificity of the inhibitors.

Secondary reference #1

Title

Interdomain motion in liver alcohol dehydrogenase. Structural and energetic analysis of the hinge bending mode.

Authors

F.Colonna-Cesari, D.Perahia, M.Karplus, H.Eklund, C.I.Brädén, O.Tapia.

Ref.

J Biol Chem, 1986, 261, 15273-15280.

PubMed id

3771574

Secondary reference #2

Title

Crystallographic investigations of nicotinamide adenine dinucleotide binding to horse liver alcohol dehydrogenase.

Authors

H.Eklund, J.P.Samama, T.A.Jones.

Ref.

Biochemistry, 1984, 23, 5982-5996. [DOI no: 10.1021/bi00320a014]

PubMed id

6098306

Secondary reference #3

Title

Pyrazole binding in crystalline binary and ternary complexes with liver alcohol dehydrogenase.

Authors

H.Eklund, J.P.Samama, L.Wallén.

Ref.

Biochemistry, 1982, 21, 4858-4866. [DOI no: 10.1021/bi00263a005]

PubMed id

6753929

Secondary reference #4

Title

Crystal structure determinations of coenzyme analogue and substrate complexes of liver alcohol dehydrogenase: binding of 1,4,5,6-Tetrahydronicotinamide adenine dinucleotide and trans-4-(N,N-Dimethylamino)cinnamaldehyde to the enzyme.

Authors

E.Cedergren-Zeppezauer, J.P.Samama, H.Eklund.

Ref.

Biochemistry, 1982, 21, 4895-4908. [DOI no: 10.1021/bi00263a011]

PubMed id

6753930

Secondary reference #5

Title

Binding of substrate in a ternary complex of horse liver alcohol dehydrogenase.

Authors

H.Eklund, B.V.Plapp, J.P.Samama, C.I.Brändén.

Ref.

J Biol Chem, 1982, 257, 14349-14358.

PubMed id

6754727

Secondary reference #6

Title

Three-Dimensional structure of horse liver alcohol dehydrogenase at 2-4 a resolution.

Authors

H.Eklund, B.Nordström, E.Zeppezauer, G.Söderlund, I.Ohlsson, T.Boiwe, B.O.Söderberg, O.Tapia, C.I.Brändén, A.Akeson.

Ref.

J Mol Biol, 1976, 102, 27-59.

PubMed id

178875

Secondary reference #7

Title

Subunit conformation of yeast alcohol dehydrogenase.

Authors

H.Jörnvall, H.Eklund, C.I.Brändén.

Ref.

J Biol Chem, 1978, 253, 8414-8419.

PubMed id

361742

Secondary reference #8

Title

The crystal structure of complexes between horse liver alcohol dehydrogenase and the coenzyme analogues 3-Iodopyridine-Adenine dinucleotide and pyridine-Adenine dinucleotide.

Authors

J.P.Samama, E.Zeppezauer, J.F.Biellmann, C.I.Brändén.

Ref.

Eur J Biochem, 1977, 81, 403-409.

PubMed id

202459

Secondary reference #9

Title

X-Ray investigation of the binding of 1,10-Phenanthroline and imidazole to horse-Liver alcohol dehydrogenase.

Authors

T.Boiwe, C.I.Bränden.

Ref.

Eur J Biochem, 1977, 77, 173-179.

PubMed id

561693

Secondary reference #10

Title

Alcohol dehydrogenases

Authors

C.-I.Branden, H.Jornvall, H.Eklund, B.Furugren.

Ref.

the enzymes,third edition, 1975, 11, 103.

Secondary reference #11

Title

Structural and functional similarities within the coenzyme binding domains of dehydrogenases.

Authors

I.Ohlsson, B.Nordström, C.I.Brändén.

Ref.

J Mol Biol, 1974, 89, 339-354. [DOI no: 10.1016/0022-2836(74)90523-3]

PubMed id

4374553

Figure 2.
FIG. 2. Three strands of parallel pleated-heet showing the arranement. of hydrogen bonds between the strands and the alignment of adjacent C/3-atoms in different strands Wc arc indebted to Bo Furugren wh designed this rawing.

Figure 3.
FIG. 3. Hydrogen-bonding diagram of p pleated-sheet region in the coenzyme binding domain of liver lcohol dehydrogenase.

The above figures are reproduced from the cited reference with permission from Elsevier

Secondary reference #12

Title

Binding of salicylate in the adenosine-Binding pocket of dehydrogenases.

Authors

R.Einarsson, H.Eklund, E.Zeppezauer, T.Boiwe, C.I.Brändén.

Ref.

Eur J Biochem, 1974, 49, 41-47.

PubMed id

4376488

Secondary reference #13

Title

The conformation of adenosine diphosphoribose and 8-Bromoadenosine diphosphoribose when bound to liver alcohol dehydrogenase.

Authors

M.A.Abdallah, J.F.Biellmann, B.Nordström, C.I.Brändén.

Ref.

Eur J Biochem, 1975, 50, 475-481.

PubMed id

163741