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. 2021 Sep 27;105(20):7661–7681. doi: 10.1007/s00253-021-11547-w

Table 1.

Microbial enzymes with 5'-nucleotidase activity

Cellular location Protein family The catalytic mechanism/initial phosphoryl acceptor Source Protein (Accession number) Substrates Metal ion requirement References
Membrane-bound / cell wall-anchored, surface-located N-terminal calcineurin-like phosphoesterase domain (Metallophos; PF00149) and C-terminal 5´-nucleotidase (5'_nucleotid_C; PF02872) domain Type I / a water molecule Staphylococcus aureus (G +) AdsA (UshA) (WP_061821283) AMP, ADP, ATP, dAMP, GDP, GTP Mg2+, Mn2+ Thammavongsa et al. 2011
Streptococcus sanguinis (G +) Nt5e (AFK32764) AMP, ADP, ATP Mg2+, Ca2+ Fan et al. 2012
Streptococcus agalactiae (G +) NudP (CDN66659) (d)NMP, (d)NDP, but not (d)NTP Mn2+ Firon et al. 2014
Streptococcus equi subsp. zooepidemicus (G +) 5Nuc (AEJ25391) AMP, ADP, ATP, dAMP Mg2+, Ca2+ Ma et al. 2016
Streptococcus pyogenes (G +) S5nA (Q9A0A2) AMP, ADP, dAMP, CMP, GMP, but not ATP Mg2+, Mn2+, Ca2+ Zheng et al. 2015
Streptococcus suis (G +) Ssads (CAR45827) AMP, ADP, ATP Mn2+ Liu et al. 2014
Streptococcus iniae (G +) S5nAi (WP_003099850) ADP, AMP, dAMP, GMP, CMP, TMP, but not ATP Mg2+, Mn2+, Ca2+ Soh et al. 2018
Bacillus anthracis (G +) AdsA (Q6HTQ7) dAMP Mn2+ Thammavongsa et al. 2009
Vibrio parahaemolyticus (G −) NutA (UshA) (P22848) AMP, ADP, ATP Cl, Mg2+, Mn2+, Co2+ Itami et al. 1989; Sakai et al. 1987
Vibrio (Salinivibrio) costicola (G −) UshA (WP_102505627) NMP, NDP, NTP Cl- Bengis-Garber and Kushner 1981
Shewanella violacea (G −) UshA (WP_041419915) AMP, ATP, GTP Mg2+, Mn2+ Kuribayashi et al. 2017
Shewanella amazonensis (G −) UshA (WP_011760134)
Class C acid phosphatase (cd07534); belong to HAD-like superfamily (IPR036412) Type II / nucleophilic amino acid residue Helicobacter pylori (G −) HppA (Q6UC93) NMP Cu2+, Ni2+, Co2+, Mg2+ Reilly and Calcutt 2004
Clostridium perfringens (G +) CppA (ACB11490) UMP, GMP, AMP, 3′ TMP, ATP, 3′ AMP, FMN, R5P, pyridoxal phosphate, ADP, 2′ AMP, NADP Cu2+, Co2+, Cr2+ Reilly et al. 2009
Chryseobacterium meningosepticum (Elizabethkingia meningoseptica) (G −) OlpA (O08351) NMP, 3′ AMP Cu2+, Mg2+ Passariello et al. 2003
Haemophilus influenzae (G −) Lipoprotein Hel [e (P4)] (WP_118891437) Aryl phosphates Cu2+ Reilly et al. 1999
Phosphoesterase family (PF04185), consists of two domains: alkaline-phosphatase-like, core domain superfamily (IPR017850) and Phosphoesterase (IPR007312) Type II / nucleophilic amino acid residue

Francisella tularensis

(G −)

AcpA (WP_003027314) NMP, NTP, NDP, FMN, NMN, NADP etc Me2+ Mohapatra et al. 2007; Reilly et al. 2006
Periplasmic N-terminal calcineurin-like phosphoesterase domain (Metallophos; PF00149) and C-terminal 5´-nucleotidase (5'_nucleotid_C; PF02872) domain Type I / a water molecule Escherichia coli (G −) UshA (P07024) (d)NTP, bis(5'-nucleosidyl)polyphosphates, UDP sugars, CDP-alcohols, NAD(H) Zn2+, Co2+or Mg2+, depending on type of hydrolase activity Alves-Pereira et al. 2008; Ruiz 1989; Glaser et al. 1967; Neu 1967; Wang et al. 2014
Vibrio cholerae (G −) UshA (Q9KQ30) dNTP - McDonough et al. 2016
Yersinia intermedia (G −) UshA (A4URQ8) (d)NTP, bis(5'-nucleosidyl)polyphosphates, UDP sugars, CDP-alcohols Co2+ or Mg2+, depending on the type of hydrolase activity Alves-Pereira et al. 2008; Neu 1967
Shewanella oneidensis (G −) UshA (Q8EFH1) FAD, AMP - Covington et al. 2010
Haemophilus influenzae (G −) NadN (P44569) AMP, NAD + , UDP sugars Zn2 +  Garavaglia et al. 2011
Klebsiella aerogenes (Enterobacter aerogenes) (G −) UshA (A0A0H3FPS2) UDP sugars - Lee et al. 2000
Class A acid phosphatase (IPR001011) Type II / nucleophilic amino acid residue Morganella morganii (Proteus morganii) (G −) PhoC (P28581) UMP, AMP, 3’-UMP, 3’-AMP - Thaller et al. 1994
Acid phosphatase class B-like (IPR005519) or HAD superfamily, subfamily IIIB (acid phosphatase) (PF03767) Morganella morganii (Proteus morganii) (G −) NapA (AphA) (Q59544) NMP, 3’ NMP, aryl phosphates, β-glycerophosphate, sugar phosphates, but not on diesters Mg2+, Co2+, Zn2+ Thaller et al. 1995
Salmonella enterica (G −) AphA (QQL85243) UMP, 3' -UMP, pNPP and a-naphthyl phosphate, but not diesters Mg2+, Co2+, Zn2+ Uerkvitz and Beck 1981
Escherichia coli (G −) AphA (P0AE22) 3'-(d)NMP, (d)NMP Mg2+ Thaller et al. 1997
Alkaline phosphatase (PF00245) Escherichia coli (G −) PhoA (P00634) Wide variety of phosphate monoesters, including 5´-ribo- and 5´-deoxyribonucleotides Mg2+, Zn2+ Garen and Levinthal 1960
Extracellular N-terminal calcineurin-like phosphoesterase domain (Metallophos; PF00149) and C-terminal 5´-nucleotidase (5'_nucleotid_C; PF02872) domain Type I / a water molecule Corynebacterium glutamicum (G +) UshA (WP_011896359) GMP, IMP, XMP, AMP, UMP, CMP, ADP, ATP, dATP Co2+, Ca2+, Mg2+, depending on the type of hydrolase activity Rittmann et al. 2005
PRK09419 Superfamily (multifunctional 2',3'-cyclic-nucleotide 2'-phosphodiesterase/3'-nucleotidase/5'-nucleotidase), contains N-terminal calcineurin-like phosphoesterase domain (Metallophos; PF00149) and C-terminal 5´-nucleotidase (5'_nucleotid_C; PF02872) domain Bacillus subtilis (G +) YfkN (BAA23404.1) 3´-nucleotides, 2′3'-cyclic-nucleotides and 5'-nucleotides - Chambert et al. 2003
Intracellular HAD-superfamily hydrolase, subfamily IIA (IPR006357) Type II / nucleophilic amino acid residue Escherichia coli (G −) YigB (P0ADP0) 5-amino-6-(5-phospho-D-ribitylamino)uracil, FMN Mg2+ Haase et al. 2013; Kuznetsova et al. 2006
Bacillus subtilis (G +) YutF (NucF) (WP_003243196) R5P, XMP, PRPP, IMP, GMP, dGMP, dIMP Mg2+ Zakataeva et al. 2016
Escherichia coli (G −) UmpH (NagD) (C3TJ42) UMP, GMP, (d)NTP, G1P Mg2+ Kuznetsova et al. 2006; Tremblay et al. 2006
HAD-superfamily hydrolase, subfamily IA (IPR006439) Escherichia coli (G −) YjjG (P0A8Y1) dTMP, dUMP, UMP, non-canonical pyrimidine derivatives (5-fluoro-2′-deoxyuridine, 5-fluorouridine, 5-fluoroorotic acid, 5-fluorouracil etc.) Mn2+, Mg2+ Kuznetsova et al., 2006; Proudfoot et al. 2004; Titz et al. 2007
Bacillus subtilis (G +) YitU (P70947) FMN, ARPP, (d)NMP (dAMP, GMP, dGMP, CMP, AMP, XMP, IMP), AICAR-P Mg2+ Sarge et al. 2015; Yusupova et al. 2020
HAD-superfamily hydrolase, subfamily IIB (IPR006379) Bacillus subtilis (G +) YcsE (P42962) ARPP, FMN, IMP, AMP, GMP, CMP, UMP, G6P Mg2+ Sarge et al. 2015; Terakawa 2016
HAD-superfamily hydrolase, subfamily IG, 5'-nucleotidase (IPR008380) Legionella pneumophila (G −) cN-II (Q5ZZB6) GMP, dGMP, IMP, pNPP Mg2+ Srinivasan et al. 2014
HD-domain phosphohydrolases (PF01966) Type I / a water molecule Escherichia coli (G −) YfbR (P76491) dNMP Co2+, Mn2+, Cu2+ Proudfoot et al. 2004; Zimmerman et al. 2008
SurE family (PF01975) or survival protein SurE (IPR030048) Type I / a water molecule Escherichia coli (G −) UmpG (SurE) (P0A840) (d) NMP, 3′-AMP, polyphosphates with the preference for short-chain-length substrates (P20–25) Mn2+, Co2+, Ni2+, Mg2+ Proudfoot et al. 2004

The abbreviations used are NMN, nicotinamide mononucleotide; FMN, flavin mononucleotide, NADP, nicotinamide adenine dinucleotide phosphate; FAD, flavin adenine dinucleotide; AICAR-P, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5′-monophosphate; ARPP, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione 5'-phosphate; G1P, glucose 1-phosphate; G6P, glucose 6-phosphate; R5P, ribose 5-phosphate; PRPP, 5-phosphoribosyl 1-pyrophosphate; pNPP, p-nitrophenyl phosphate; (d)NMP/(d)NDP/(d)NTP, ribonucleoside or deoxyribonucleoside mono-, di- and triphosphates. The accession numbers correspond to the UniProt or NCBI databases; (G −) and (G +)—gram-negative and gram-positive bacteria; –—not found