2 Evolutionary and Structural Relationships among Dehydrogenases

Rossman, Michael G.; Liljas, Anders; Brändén, Carl‐Ivar; Banaszak, Leonard J.

doi:10.1016/s1874-6047(08)60210-3

Cited by 615 publications

(457 citation statements)

References 72 publications

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“…Overall description of secondary and tertiary structure A ribbon plot (Priestle, 1988) of the molecule is shown in Figure 4 (see also Kinemage 1). The structure is built around a five-stranded parallel &sheet core with a pair of helices flanking on either side, typical of nucleotide binding folds (Rossmann et al, 1975). FMN binds at the southern edge of the molecule and interacts with residues in the loops between the strands and with the N-terminal residues of the a,-helix.…”

Section: Resultsmentioning

confidence: 99%

Structure of the oxidized long‐chain flavodoxin from anabaena 7120 at 2 å resolution

et al. 1992

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The structure of the long-chain flavodoxin from the photosynthetic cyanobacterium Anabaena 7120 has been determined at 2 A resolution by the molecular replacement method using the atomic coordinates of the long-chain flavodoxin from Anacystis nidulans. The structure of a third long-chain flavodoxin from Chondrus crispus has recently been reported. Crystals of oxidized A . 7120 flavodoxin belong to the monoclinic space group P2, with a = 48.0, b = 32.0, c = 51.6A, and 0 = 92", and one molecule in the asymmetric unit. The 2 A intensity data were collected with oscillation films at the CHESS synchrotron source and processed to yield 9,795 independent intensities with Rmerg of 0.07. Of these, 8,493 reflections had I > 2a and were used in the analysis. The model obtained by molecular replacement was initially refined by simulated annealing using the XPLOR program. Repeated refitting into omit maps and several rounds of conjugate gradient refinement led to an R-value of 0.185 for a model containing atoms for protein residues 2-169, flavin mononucleotide (FMN), and 104 solvent molecules. The FMN shows many interactions with the protein with the isoalloxazine ring, ribityl sugar, and the 5'-phosphate. The flavin ring has its pyrimidine end buried into the protein, and the functional dimethyl benzene edge is accessible to solvent. The FMN interactions in all three long-chain structures are similar except for the 04' of the ribityl chain, which interacts with the hydroxyl group of Thr 88 side chain in A. 7120, while with a water molecule in the other two. The phosphate group interacts with the atoms of the 9-15 loop as well as with NE1 of Trp 57. The N5 atom of flavin interacts with the amide NH of Ile 59 in A . 7120, whereas in A . nidulans it interacts with the amide NH of Val 59 in a similar manner. In C. crispus flavodoxin, N5 forms a hydrogen bond with the side chain hydroxyl group of the equivalent Thr 58. The hydrogen bond distances to the backbone NH groups in the first two flavodoxins are 3.6 A and 3.5 A , respectively, whereas in the third flavodoxin the distance is 3.1 A , close to the normal value. Even though the hydrogen bond distances are long in the first two cases, still they might have significant energy because their microenvironment in the protein is not accessible to solvent. In all three long-chain flavodoxins, a water molecule bridges the ends of the inserted loop in the os strand and minimally perturbs its hydrogen bonding with p4. Many of the water molecules in these proteins interact with the flavin binding loops. The conserved &core of the three long-chain and two short-chain flavodoxins superpose with root mean square deviations ranging from 0.48 A to 0.97 A .

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Section: Resultsmentioning

confidence: 99%

Structure of the oxidized long‐chain flavodoxin from anabaena 7120 at 2 å resolution

et al. 1992

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“…The NAD+-binding domains of many enzymes possess a common flap fold [22] centred around a highly conserved sequence Gly-Xaa-Gly-Xaa-Xaa-Gly that constitutes a tight turn between the first strand of a fl-sheet and the start of the following cr-helix 1231. In several NADP' -dependent dehydrogenases, the same fingerprint region can be discerned, albeit with some differences [23 -251.…”

Section: Resultsmentioning

confidence: 99%

6‐Deoxyerythronolide‐B synthase 2 from Saccharopolyspora erythraea

Bevitt

Cortés

Haydock

et al. 1992

European Journal of Biochemistry

170

101

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Sequencing of the eryA region of the erythromycin biosynthetic gene cluster from Saccharopolyspora erythraea has revealed another structural gene (ORF B), in addition to the previously characterised ORF A , which appears to encode a component of 6-deoxyerythronolide-B synthase, the enzyme that catalyses the first stage in the biosynthesis of the polyketide antibiotic erythromycin A. The nucleotide sequence of ORF B, whch lies immediately adjacent to ORF A , has been determined. The predicted gene product of ORF B is a polypeptide of 374417 Da (3568 amino acids), which is highly similar to the product of ORF A and which likewise contains a number of separate domains, each with substantial amino acid sequence similarity to components of known fatty-acid synthases and polyketide synthases. The order of the predicted active sites along the chain from the N-terminus is 3-oxoacyl-synthase -acyltransferase -acyl-carrier-protein -3-oxoacyl-synthase -acyltransferase -dehydratase -enoylreductase -oxoreductase -acyl-carrier-protein. The position of the dehydratase active site has been pinpointed for the first time for any polyketide synthase or vertebrate fatty-acid synthase. The predicted domain structure of 6-deoxyerythronolide-B synthase is strikingly similar to that previously established for vertebrate fatty-acid synthases. This analysis of the sequence supports the view that the erythromycin-producing polyketide synthase contains three multienzyme polypeptides, each of which accomplishes two successive cycles of polyketide chain extension. In this scheme, the role of the ORF B gene product is to accomplish extension cycles 3 and 4.

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“…Acharacteristic feature of these folds is the presence of a P-sheet, parallel or antiparallel, in the vicinity of the ATP-binding site. One class of folds, the classic mononucleotide-binding fold (Schulz & Schirmer, 1974;Rossmann et al, 1975;Schulz et al, 1986), has an ATP-binding site placed at the edge of a parallel P-sheet. Two other classes of folds, the protein kinase family fold (Hanks et al, 1988;Hanks & Quinn, 1991;Hubbard et al, 1994;Xu et al, 1995), and the glutathione synthetase fold (Yamaguchi et al, 1993;Waldrop et al, 1994;Wolodko et al, 1994;Fan et al, 1995;Artymiuk et al, 1996;Herzberg et al, 1996;Hibi et al, 1996;Matsuda et al, 1996;Thoden et al, 1997;Esser et 1998), also called the "ATP-grasp'' fold (Murzin, 1996), have ATPbinding sites positioned on the surface of an antiparallel &sheet (Kobayashi & Go, 1997b).…”

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Enzyme‐mononucleotide interactions: Three different folds share common structural elements for atp recognition

1998

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Three ATP-dependent enzymes with different folds, CAMP-dependent protein kinase, D-Ala:o-Ala ligase and the a-subunit of the a2P2 ribonucleotide reductase, have a similar organization of their ATP-binding sites. The most meaningful similarity was found over 23 structurally equivalent residues in each protein and includes three strands each from their @sheets, in addition to a connecting loop. The equivalent secondary structure elements in each of these enzymes donate four amino acids forming key hydrogen bonds responsible for the common orientation of the "AMP" moieties of their ATP-ligands. One lysine residue conserved throughout the three families binds the alpha-phosphate in each protein. The common fragments of structure also position some, but not all, of the equivalent residues involved in hydrophobic contacts with the adenine ring. These examples of convergent evolution reinforce the view that different proteins can fold in different ways to produce similar structures locally, and nature can take advantage of these features when structure and function demand it, as shown here for the common mode of ATP-binding by three unrelated proteins.Keywords: allosteric effector-binding site; ATP-dependent enzymes; convergent structural similarities; local structural comparisons; similar ligand-binding sites Adenosine 5"triphosphate (ATP) is necessary for the function of a wide variety of enzymes. Currently, the Brookhaven Protein Data Bank (PDB) (Bernstein et al., 1977) contains atomic coordinates for over 140 X-ray and NMR structures of ATP-dependent proteins solved as complexes mainly with bound ATP-analogues, bound AMP, bound ADP, and in some cases with bound ATP.Several distinct classes of folds of ATP-dependent enzymes have been identified (Schulz, 1992). Acharacteristic feature of these folds is the presence of a P-sheet, parallel or antiparallel, in the vicinity of the ATP-binding site. One class of folds, the classic mononucleotide-binding fold (Schulz & Schirmer, 1974;Rossmann et al., 1975;Schulz et al., 1986), has an ATP-binding site placed at the edge of a parallel P-sheet. Two other classes of folds, the protein kinase family fold (Hanks et al

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2 Evolutionary and Structural Relationships among Dehydrogenases

Cited by 615 publications

References 72 publications

Structure of the oxidized long‐chain flavodoxin from anabaena 7120 at 2 å resolution

Structure of the oxidized long‐chain flavodoxin from anabaena 7120 at 2 å resolution

6‐Deoxyerythronolide‐B synthase 2 from Saccharopolyspora erythraea

Enzyme‐mononucleotide interactions: Three different folds share common structural elements for atp recognition

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