Molecular symmetry axes and subunit interfaces in certain dehydrogenases

Rossmann, Michael G.; Adams, Margaret; Buehner, Manfred; Ford, Geoffrey C.; Hackert, Marvin L.; Liljas, Anders; Rao, S.T.; Banaszak, Leonabd J.; Hill, Edward J.; Tsernoglou, Demetrius; Webb, Laurence

doi:10.1016/0022-2836(73)90491-9

Cited by 92 publications

(38 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the structural heterodimer of Ps3␣HSD, the apo-and holo-subunits interact with each other in the region 217-255, which includes the ␤G strand, the helix ␣G, and the C-terminal helix ␣CT, in the manner of the P-interface in tetrameric SDRs (8,24). This dimer interface is supported by the following specific interactions.…”

Section: Resultsmentioning

confidence: 99%

Apo- and Holo-structures of 3α-Hydroxysteroid Dehydrogenase fromPseudomonassp. B-0831

et al. 2006

View full text Add to dashboard Cite

Bacterial 3␣-hydroxysteroid dehydrogenase, which belongs to a short-chain dehydrogenase/reductase family and forms a dimer composed of two 26-kDa subunits, catalyzes the oxidoreduction of hydroxysteroids in a coenzyme-dependent manner. This enzyme also catalyzes the oxidoreduction of nonsteroid compounds that play an important role in xenobiotic metabolism of bacteria. We performed an x-ray analysis on the crystal of Ps3␣HSD, the enzyme from Pseudomonas sp. B-0831 complexed with NADH. The resulting crystal structure at 1.8 Å resolution showed that Ps3␣HSD exists as a structural heterodimer composed of apo-and holo-subunits. A distinct structural difference between them was found in the 185-207-amino acid region, where the structure in the apo-subunit is disordered whereas that in the holo-subunit consists of two ␣-helices. This fact proved that the NADH binding allows the helical structures to form the substrate binding pocket even in the absence of the substrate, although the region corresponds to the so-called "substrate-binding loop." The induction of ␣-helices in solution by the coenzyme binding was also confirmed by the CD experiment. In addition, the CD experiment revealed that the helixinducing ability of NADH is stronger than that of NAD. We discuss the negative cooperativity for the coenzyme binding, which is caused by the effect of the structural change transferred between the subunits of the heterodimer.Hydroxysteroid dehydrogenases are classified into three superfamilies as follows: aldo-keto reductase, long/mediumchain dehydrogenase/reductase, and short-chain dehydrogenase/reductase (SDR).2 Bacterial 3␣-hydroxysteroid dehydrogenase from Pseudomonas sp. B-0831 (Ps3␣HSD, EC 1.1.1.50) belonging to the SDR family forms a dimer composed of two 26-kDa subunits and catalyzes the oxidoreduction of steroid compounds as the reversible inter-conversion between 3␣-hydroxysteroid and 3-ketosteroid. In addition, Ps3␣HSD can also catalyze the oxidoreduction of nonsteroid compounds, such as p-nitrobenzaldehyde, and therefore is also named as 3␣-hydroxysteroid dehydrogenase/carbonyl reductase (3␣HSD/CR) (1). Bacteria are supposed to use this 3␣HSD/CR activity for a xenobiotic metabolism that is the first step in the consecutive detoxification process in bacterial organisms (2, 3). The enzymes belonging to the SDR family form a common tertiary structure of a dinucleotide-binding motif, popularly known as the Rossmann fold (4). These structures have the same architecture as the Ser-Tyr-Lys triad (SYK triad) as an active site and the same coenzyme-binding motif GXXXGXG at the N-terminal region. Although they have quite similar coenzyme-binding sites, there is a unique specificity for NAD(H) and/or NADP(H). A number of studies have been performed to explain the coenzyme specificity in SDR and illuminated that the Asp residue at the coenzyme-binding site determines the preference of NAD(H). The switch of the coenzyme preference from NADP(H) to NAD(H) has been achieved by the mutation of this Asp residue (5). We have stud...

show abstract

Section: Resultsmentioning

confidence: 99%

Apo- and Holo-structures of 3α-Hydroxysteroid Dehydrogenase fromPseudomonassp. B-0831

et al. 2006

View full text Add to dashboard Cite

show abstract

“…As per the conventional nomenclature of SDR enzymes, the subunit contacts are named based on the three perpendicular axes P, Q, and R along the tetrameric arrangement of monomers (30). In BphB B-356 , the monomers in an asymmetric unit coincide by the P axis.…”

Section: Quality Of Thementioning

confidence: 99%

Biochemical Studies and Ligand-bound Structures of Biphenyl Dehydrogenase from Pandoraea pnomenusa Strain B-356 Reveal a Basis for Broad Specificity of the Enzyme

Dhindwal

Patil

Mohammadi

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: BphB B-356 catalyzes the second step of the PCB catabolic pathway. Result: Apo, binary, intermediate, and ternary structures were obtained. Conclusion: Conformational changes in the substrate binding loop lead to the formation of a structurally defined pocket to catalyze a wide range of substrates. Significance: Recognition of conformational changes in the substrate binding loop and insight into the substrate specificity.

show abstract

“…2). The subunit-subunit interactions across the molecular 2-fold axis labeled Q in lactate dehydrogenase (20) have essentially been maintained, as in malate dehydrogenase (ref. 21; and see below).…”

mentioning

confidence: 99%

D-Glyceraldehyde-3-Phosphate Dehydrogenase: Three-Dimensional Structure and Evolutionary Significance

Buehner

Ford

Moras

et al. 1973

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

156

View full text Add to dashboard Cite

show abstract

Molecular symmetry axes and subunit interfaces in certain dehydrogenases

Cited by 92 publications

References 6 publications

Apo- and Holo-structures of 3α-Hydroxysteroid Dehydrogenase fromPseudomonassp. B-0831

Apo- and Holo-structures of 3α-Hydroxysteroid Dehydrogenase fromPseudomonassp. B-0831

Biochemical Studies and Ligand-bound Structures of Biphenyl Dehydrogenase from Pandoraea pnomenusa Strain B-356 Reveal a Basis for Broad Specificity of the Enzyme

D-Glyceraldehyde-3-Phosphate Dehydrogenase: Three-Dimensional Structure and Evolutionary Significance

Contact Info

Product

Resources

About