PDBsum entry 1adb

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

PDB id: 1adb

Contents

Protein chains

374 a.a. *

Ligands

CND ×2

EOH ×2

Metals

_ZN ×4

Waters ×264

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystallographic studies of isosteric NAD analogues bound to alcohol dehydrogenase: specificity and substrate binding in two ternary complexes.

Authors

H.Li, W.H.Hallows, J.S.Punzi, K.W.Pankiewicz, K.A.Watanabe, B.M.Goldstein.

Ref.

Biochemistry, 1994, 33, 11734-11744. [DOI no: 10.1021/bi00205a009]

PubMed id

7918390

Abstract

CNAD (5-beta-D-ribofuranosylnicotinamide adenine dinucleotide) is an isosteric C-glycosidic analogue of NAD(H) containing a neutral pyridine ring. CPAD (5-beta-D-ribofuranosylpicolinamide adenine dinucleotide) is a closely related pyridine-containing analogue with the pyridine nitrogen on the opposite side of the ring. CNAD is a potent and specific inhibitor of horse liver alcohol dehydrogenase (LADH), binding with a dissociation constant in the nanomolar range. CPAD binds LADH with an affinity comparable to that of NAD. Crystal structures of CNAD and CPAD bound to LADH are presented at 2.4 and 2.7 A, respectively. The two complexes are isomorphous, crystallizing in the triclinic system with cell dimensions different from those seen in previous ternary LADH complexes. Structures were solved using the molecular replacement method and refined to crystallographic R values of 18% (CNAD) and 17% (CPAD). Both inhibitors bind to the "closed" form of LADH in the normal cofactor-binding cleft. The conformation of LADH-bound CPAD closely mimics that of LADH-bound NAD(H). The data suggest that alcohol substrate binds directly to the catalytic zinc atom. In the CNAD complex, the pyridine nitrogen replaces alcohol as the fourth coordination ligand to the active site zinc atom, while all other polar interactions remain the same as those of bound NAD(H). The zinc-nitrogen ligand explains the high affinity of CNAD for LADH.

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

Crystal structures of the active site in specifically metal-Depleted and cobalt-Substituted horse liver alcohol dehydrogenase derivatives.

Authors

G.Schneider, H.Eklund, E.Cedergren-Zeppezauer, M.Zeppezauer.

Ref.

Proc Natl Acad Sci U S A, 1983, 80, 5289-5293. [DOI no: 10.1073/pnas.80.17.5289]

PubMed id

6351056

Secondary reference #4

Title

Three-Dimensional structure of isonicotinimidylated liver alcohol dehydrogenase.

Authors

B.V.Plapp, H.Eklund, T.A.Jones, C.I.Brändén.

Ref.

J Biol Chem, 1983, 258, 5537-5547.

PubMed id

6343388

Secondary reference #5

Title

Crystal-Structure determination of reduced nicotinamide adenine dinucleotide complex with horse liver alcohol dehydrogenase maintained in its apo conformation by zinc-Bound imidazole.

Author

E.Cedergren-Zeppezauer.

Ref.

Biochemistry, 1983, 22, 5761-5772. [DOI no: 10.1021/bi00294a013]

PubMed id

6362718

Secondary reference #6

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 #7

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 #8

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 #9

Title

5-Methylnicotinamide-Adenine dinucleotide. Kinetic investigation with major and minor isoenzymes of liver alcohol dehydrogenase and structural determination of its binary complex with alcohol dehydrogenase.

Authors

J.P.Samama, A.D.Wrixon, J.F.Biellmann.

Ref.

Eur J Biochem, 1981, 118, 479-486.

PubMed id

7028480

Secondary reference #10

Title

Structural differences between apo- And holoenzyme of horse liver alcohol dehydrogenase.

Authors

H.Eklund, C.I.Brändén.

Ref.

J Biol Chem, 1979, 254, 3458-3461.

PubMed id

218969

Secondary reference #11

Title

X-Ray studies of the binding of cibacron blue f3ga to liver alcohol dehydrogenase.

Authors

J.F.Biellmann, J.P.Samama, C.I.Bränden, H.Eklund.

Ref.

Eur J Biochem, 1979, 102, 107-110.

PubMed id

520314

Secondary reference #12

Title

Crystallography of liver alcohol dehydrogenase complexed with substrates.

Authors

B.V.Plapp, H.Eklund, C.I.Brändén.

Ref.

J Mol Biol, 1978, 122, 23-32.

PubMed id

209195

Secondary reference #13

Title

Crystallization of liver alcohol dehydrogenase activated by the modification of amino groups.

Authors

B.V.Plapp, E.Zeppezauer, C.I.Brändém.

Ref.

J Mol Biol, 1978, 119, 451-453. [DOI no: 10.1016/0022-2836(78)90225-5]

PubMed id

641997

Figure 1.
FIG. I. Crystallography of isonicotinimidylated liver alcohol dehydrogenare. (a) Photomicro graph of crystals prpared by dialysl `5 against 0.05 M-Tris.HCl (pH 8.4), 5°C. The longest crystal diagonal (parallel to n axis) is about 0.25 mm. (b) hk0 projection, b* vertical, n* horizontal, X-ray beam impinging onto diamond-shaped face (c) h01 projection, a* horizontal, c* inclined at angle of 76' toward uppe right.. (d) OkZ projection, h * horizontal, c* vertical. The precession photo- graphs (CL = 9'') were exposed for 21 h at. 5°C. using Ni-filtered &Ku radiation, with a crystal- to-film distance of 75 mm. The prints arc about actual size.

The above figure is reproduced from the cited reference with permission from Elsevier

Secondary reference #14

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 #15

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 #16

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 #17

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 #18

Title

Structural comparisons of mammalian, Yeast and bacillar alcohol dehydrogenases.

Authors

H.Eklund, C.I.Brändén, H.Jörnvall.

Ref.

J Mol Biol, 1976, 102, 61-73.

PubMed id

775100

Secondary reference #19

Title

The binding of nucleotides to horse liver alcohol dehydrogenase

Authors

B.Nordstrom, C.-I.Branden.

Ref.

structure and conformation ...

Secondary reference #20

Title

Alcohol dehydrogenases

Authors

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

Ref.

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

Secondary reference #21

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

Secondary reference #22

Title

The structure of horse liver alcohol dehydrogenase.

Authors

H.Eklund, B.Nordström, E.Zeppezauer, G.Söderlund, I.Ohlsson, T.Boiwe, C.I.Brändén.

Ref.

Febs Lett, 1974, 44, 200-204. [DOI no: 10.1016/0014-5793(74)80725-8]

PubMed id

4473096

Figure 2.
Fig. 2. Sereo diagra of the coenzyme-binding domain of LADH (dark bonds) superimposed on the corresponding region of

Figure 3.
Fig. 3. Schematic diagram illustrating he interactions between ADP-ribose and LADH. We are indebted to Bo Furugren who e-

The above figures are reproduced from the cited reference with permission from the Federation of European Biochemical Societies

Secondary reference #23

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 #24

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 #25

Title

Structure of liver alcohol dehydrogenase at 2.9-Angstrom resolution.

Authors

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

Ref.

Proc Natl Acad Sci U S A, 1973, 70, 2439-2442. [DOI no: 10.1073/pnas.70.8.2439]

PubMed id

4365379

Secondary reference #26

Title

Structure of horse liver alcohol dehydrogenase. I. Structural symmetry and conformational changes

Author

C.-I.Branden.

Ref.

atlas of protein sequence, 1972, 5, 145.