Amidohydrolase Superfamily

The amidohydrolase superfamily is a structure-based cluster of enzymes that contain a sturdy and versatile triosephosphate isomerase (TIM)-like (β/α)₈-barrel fold embracing the catalytic active site. To date, the amidohydrolase superfamily has grown into one of the largest families of enzymes, with tens of thousand of members catalysing a wide range of hydrolytic and nonhydrolytic metabolic reactions which are important in amino acid and nucleotide metabolism as well as biodegradation of agricultural and industrial compounds. Previously, the presence of a mono- or dinuclear d-block metal cofactor in the active site was thought to be one of the main characteristics of the members in this superfamily. However, recently new members containing a trinuclear metal cofactors or no cofactor at all were discovered. It has become apparent that activating a well-ordered water molecule by an active site residue for nucleophilic attack on the organic substrate is a common mechanistic feature for all members of the superfamily.

Key Concepts:

Amidohydrolase superfamily is one of the largest enzyme superfamilies performing a wide array of catalytic reactions.
All members in the family employ a TIM-barrel structural fold, although some of the amidohydrolase superfamily members present an imperfect barrel.
The vast majority, but not all, of the enzymes in this superfamily are metalloenzymes.
The hallmark of the catalytic mechanisms shared by these enzymes is to use an activated water molecule to attack the organic substrate.
The catalytic centre is diverse, with one, two, three or zero metal ion(s).

References

Alhapel A, Darley DJ, Wagener N et al. (2006) Molecular and functional analysis of nicotinate catabolism in Eubacterium barkeri . Proceedings of the National Academy of Sciences USA 103: 12341–12346.
10.1073/pnas.0601635103
CAS PubMed Web of Science® Google Scholar
Buchan DW, Ward SM, Lobley AE et al. (2010) Protein structure prediction servers at University College London. Nucleic Acids Research 38: W563–W568.
10.1093/nar/gkq427
CAS PubMed Web of Science® Google Scholar
Finn RD, Bateman A, Clements J et al. (2014) The Pfam protein families database. Nucleic Acids Research 42: D222–D230.
10.1093/nar/gkt1223
CAS PubMed Web of Science® Google Scholar
Ghodge SV, Fedorov AA, Fedorov EV et al. (2013) Structural and mechanistic characterization of l-histidinol phosphate phosphatase from the polymerase and histidinol phosphatase family of proteins. Biochemistry 52: 1101–1112.
10.1021/bi301496p
CAS PubMed Web of Science® Google Scholar
Goto M, Hayashi H, Miyahara I et al. (2006) Crystal structures of nonoxidative zinc-dependent 2,6-dihydroxybenzoate (γ-resorcylate) decarboxylase from Rhizobium sp. strain MTP-10005. Journal of Biological Chemistry 281: 34365–34373.
10.1074/jbc.M607270200
CAS PubMed Web of Science® Google Scholar
Hagelueken G, Huang H, Mainprize IL, Whitfield C and Naismith JH (2009) Crystal structures of Wzb of Escherichia coli and CpsB of Streptococcus pneumoniae, representatives of two families of tyrosine phosphatases that regulate capsule assembly. Journal of Molecular Biology 392: 678–688.
10.1016/j.jmb.2009.07.026
CAS PubMed Web of Science® Google Scholar
Han BW, Bingman CA, Mahnke DK et al. (2006) Membrane association, mechanism of action, and structure of Arabidopsis embryonic factor 1 (FAC1). Journal of Biological Chemistry 281: 14939–14947.
10.1074/jbc.M513009200
CAS PubMed Web of Science® Google Scholar
Hobbs ME, Malashkevich V, Williams HJ et al. (2012) Structure and catalytic mechanism of LigI: insight into the amidohydrolase enzymes of cog3618 and lignin degradation. Biochemistry 51: 3497–3507.
10.1021/bi300307b
CAS PubMed Web of Science® Google Scholar
Hobbs ME, Vetting M, Williams HJ et al. (2013) Discovery of an l-fucono-1,5-lactonase from cog3618 of the amidohydrolase superfamily. Biochemistry 52: 239–253.
10.1021/bi3015554
CAS PubMed Web of Science® Google Scholar
Holm L and Sander C (1997) An evolutionary treasure: unification of a broad set of amidohydrolases related to urease. Proteins 28: 72–82.
10.1002/(SICI)1097-0134(199705)28:1<72::AID-PROT7>3.0.CO;2-L
CAS PubMed Web of Science® Google Scholar
Huo L, Davis I, Chen L and Liu A (2013) The power of two: arginine 51 and arginine 239^* from a neighboring subunit are essential for catalysis in α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase. Journal of Biological Chemistry 288: 30862–30871.
10.1074/jbc.M113.496869
CAS PubMed Web of Science® Google Scholar
Huo L, Fielding AJ, Chen Y et al. (2012) Evidence for a dual role of an active site histidine in α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase. Biochemistry 51: 5811–5821.
10.1021/bi300635b
CAS PubMed Web of Science® Google Scholar
Kim HS, Lee SJ, Yoon HJ et al. (2011) Crystal structures of YwqE from Bacillus subtilis and CpsB from Streptococcus pneumoniae, unique metal-dependent tyrosine phosphatases. Journal of Structural Biology 175: 442–450.
10.1016/j.jsb.2011.05.007
CAS PubMed Web of Science® Google Scholar
Li T, Iwaki H, Fu R et al. (2006) α-Amino-β-carboxymuconic-ϵ-semialdehyde decarboxylase (ACMSD) is a new member of the amidohydrolase superfamily. Biochemistry 45: 6628–6634.
10.1021/bi060108c
CAS PubMed Web of Science® Google Scholar
Li T, Lu H, Pulley C and Liu A (2012) Decarboxylation mechanisms in biological system. Bioorganic Chemistry 43: 2–14.
10.1016/j.bioorg.2012.03.001
CAS PubMed Web of Science® Google Scholar
Li T, Ma J, Hosler JP, Davidson VL and Liu A (2007) Detection of transient intermediates in the metal-dependent non-oxidative decarboxylation catalyzed by α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase. Journal of the American Chemical Society 129: 9278–9279.
10.1021/ja073648l
CAS PubMed Web of Science® Google Scholar
Li T, Walker AL, Iwaki H, Hasegawa Y and Liu A (2005) Kinetic and spectroscopic characterization of ACMSD from Pseudomonas fluorescens reveals a pentacoordinate mononuclear metallocofactor. Journal of the American Chemical Society 127: 12282–12290.
10.1021/ja0532234
CAS PubMed Web of Science® Google Scholar
Liu A and Zhang H (2006) Transition metal-catalyzed nonoxidative decarboxylation reactions. Biochemistry 45: 10407–10411.
10.1021/bi061031v
CAS PubMed Web of Science® Google Scholar
Nguyen TT, Brown S, Fedorov AA et al. (2008) At the periphery of the amidohydrolase superfamily: Bh0493 from Bacillus halodurans catalyzes the isomerization of d-galacturonate to d-tagaturonate. Biochemistry 47: 1194–1206.
10.1021/bi7017738
CAS PubMed Web of Science® Google Scholar
Nguyen TT, Fedorov AA, Williams L et al. (2009) The mechanism of the reaction catalyzed by uronate isomerase illustrates how an isomerase may have evolved from a hydrolase within the amidohydrolase superfamily. Biochemistry 48: 8879–8890.
10.1021/bi901046x
CAS PubMed Web of Science® Google Scholar
Seffernick JL, de Souza ML, Sadowsky MJ and Wackett LP (2001) Melamine deaminase and atrazine chlorohydrolase: 98 percent identical but functionally different. Journal of Bacteriology 183: 2405–2410.
10.1128/JB.183.8.2405-2410.2001
CAS PubMed Web of Science® Google Scholar
Seibert CM and Raushel FM (2005) Structural and catalytic diversity within the amidohydrolase superfamily. Biochemistry 44: 6383–6391.
10.1021/bi047326v
CAS PubMed Web of Science® Google Scholar
Serner R and Höcker B (2005) Catalytic versatility, stability, and evolution of the (βα)8-barrel enzyme fold. Chemical Reviews 105: 4038–4055.
10.1021/cr030191z
CAS PubMed Web of Science® Google Scholar
Williams L, Nguyen T, Li Y, Porter TN and Raushel FM (2006) Uronate isomerase: a nonhydrolytic member of the amidohydrolase superfamily with an ambivalent requirement for a divalent metal ion. Biochemistry 45: 7453–7462.
10.1021/bi060531l
CAS PubMed Web of Science® Google Scholar
Xu S, Li W, Zhu J et al. (2013) Crystal structures of isoorotate decarboxylases reveal a novel catalytic mechanism of 5-carboxyl-uracil decarboxylation and shed light on the search for DNA decarboxylase. Cell Research 23: 1296–1309.
10.1038/cr.2013.107
CAS PubMed Web of Science® Google Scholar

Citing Literature

eLS

Browse other articles of this reference work: