cd05372

Enoyl acyl carrier protein (ACP) reductase (ENR), divergent SDR

CDD entry
Member databaseCDD
CDD typedomain
Short nameENR_SDR
SetNADB_Rossmann

Description

This bacterial subgroup of ENRs includes Escherichia coli ENR. ENR catalyzes the NAD(P)H-dependent reduction of enoyl-ACP in the last step of fatty acid biosynthesis. De novo fatty acid biosynthesis is catalyzed by the fatty acid synthetase complex, through the serial addition of 2-carbon subunits. In bacteria and plants,ENR catalyzes one of six synthetic steps in this process. Oilseed rape ENR, and also apparently the NADH-specific form of Escherichia coli ENR, is tetrameric. Although similar to the classical SDRs, this group does not have the canonical catalytic tetrad, nor does it have the typical Gly-rich NAD-binding pattern. Such so-called divergent SDRs have a GXXXXXSXA NAD-binding motif and a YXXMXXXK (or YXXXMXXXK) active site motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.
[12, 4, 8, 11, 9, 5, 2, 7, 10, 6, 1, 3]

References

1.GXXXG and GXXXA motifs stabilize FAD and NAD(P)-binding Rossmann folds through C(alpha)-H... O hydrogen bonds and van der waals interactions. Kleiger G, Eisenberg D. J. Mol. Biol. 323, 69-76, (2002). PMID: 12368099

2.Short-chain dehydrogenases/reductases (SDR). Jornvall H, Persson B, Krook M, Atrian S, Gonzalez-Duarte R, Jeffery J, Ghosh D. Biochemistry 34, 6003-13, (1995). View articlePMID: 7742302

3.Medium- and short-chain dehydrogenase/reductase gene and protein families : Structure-function relationships in short-chain alcohol dehydrogenases. Ladenstein R, Winberg JO, Benach J. Cell. Mol. Life Sci. 65, 3918-35, (2008). View articlePMID: 19011748

4.Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan. Ward WH, Holdgate GA, Rowsell S, McLean EG, Pauptit RA, Clayton E, Nichols WW, Colls JG, Minshull CA, Jude DA, Mistry A, Timms D, Camble R, Hales NJ, Britton CJ, Taylor IW. Biochemistry 38, 12514-25, (1999). View articlePMID: 10493822

5.Short-chain dehydrogenases/reductases (SDR): the 2002 update. Oppermann U, Filling C, Hult M, Shafqat N, Wu X, Lindh M, Shafqat J, Nordling E, Kallberg Y, Persson B, Jornvall H. Chem. Biol. Interact. 143-144, 247-53, (2003). View articlePMID: 12604210

6.Short-chain dehydrogenase/reductase (SDR) relationships: a large family with eight clusters common to human, animal, and plant genomes. Kallberg Y, Oppermann U, Jornvall H, Persson B. Protein Sci 11, 636-41, (2002). PMID: 11847285

7.NAD-binding domains of dehydrogenases. Lesk AM. Curr. Opin. Struct. Biol. 5, 775-83, (1995). View articlePMID: 8749365

8.Crystallization of the NADH-specific enoyl acyl carrier protein reductase from Brassica napus. Rafferty JB, Simon JW, Stuitje AR, Slabas AR, Fawcett T, Rice DW. J Mol Biol 237, 240-2, (1994). PMID: 8126737

9.Coenzyme-based functional assignments of short-chain dehydrogenases/reductases (SDRs). Persson B, Kallberg Y, Oppermann U, Jornvall H. Chem. Biol. Interact. 143-144, 271-8, (2003). View articlePMID: 12604213

10.Medium- and short-chain dehydrogenase/reductase gene and protein families : the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Kavanagh KL, Jornvall H, Persson B, Oppermann U. Cell. Mol. Life Sci. 65, 3895-906, (2008). View articlePMID: 19011750

11.Common themes in redox chemistry emerge from the X-ray structure of oilseed rape (Brassica napus) enoyl acyl carrier protein reductase. Rafferty JB, Simon JW, Baldock C, Artymiuk PJ, Baker PJ, Stuitje AR, Slabas AR, Rice DW. Structure 3, 927-38, (1995). View articlePMID: 8535786

12.Diversity in enoyl-acyl carrier protein reductases. Massengo-Tiasse RP, Cronan JE. Cell Mol Life Sci 66, 1507-17, (2009). PMID: 19151923

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