PDBsum entry 1ilw

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protein links
Hydrolase PDB id
Protein chain
179 a.a. *
Waters ×88
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of pyrazinamidase/nicotinamidase of pyrococcus horikoshii
Structure: 180 aa long hypothetical pyrazinamidase/nicotinamidase. Chain: a. Engineered: yes
Source: Pyrococcus horikoshii. Organism_taxid: 53953. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.05Å     R-factor:   0.189     R-free:   0.257
Authors: X.Du,S.-H.Kim,Berkeley Structural Genomics Center (Bsgc)
Key ref:
X.Du et al. (2001). Crystal structure and mechanism of catalysis of a pyrazinamidase from Pyrococcus horikoshii. Biochemistry, 40, 14166-14172. PubMed id: 11714269 DOI: 10.1021/bi0115479
08-May-01     Release date:   12-Dec-01    
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Protein chain
Pfam   ArchSchema ?
O58727  (O58727_PYRHO) -  180aa long hypothetical pyrazinamidase/nicotinamidase
180 a.a.
179 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     catalytic activity     2 terms  


DOI no: 10.1021/bi0115479 Biochemistry 40:14166-14172 (2001)
PubMed id: 11714269  
Crystal structure and mechanism of catalysis of a pyrazinamidase from Pyrococcus horikoshii.
X.Du, W.Wang, R.Kim, H.Yakota, H.Nguyen, S.H.Kim.
Bacterial pyrazinamidase (PZAase)/nicotinamidase converts pyrazinamide (PZA) to ammonia and pyrazinoic acid, which is active against Mycobacterium tuberculosis. Loss of PZAase activity is the major mechanism of pyrazinamide-resistance by M. tuberculosis. We have determined the crystal structure of the gene product of Pyrococcus horikoshii 999 (PH999), a PZAase, and its complex with zinc ion by X-ray crystallography. The overall fold of PH999 is similar to that of N-carbamoylsarcosine amidohydrolase (CSHase) of Arthrobacter sp. and YcaC of Escherichia coli, a protein with unknown physiological function. The active site of PH999 was identified by structural features that are also present in the active sites of CSHase and YcaC: a triad (D10, K94, and C133) and a cis-peptide (between V128 and A129). Surprisingly, a metal ion-binding site was revealed in the active site and subsequently confirmed by crystal structure of PH999 in complex with Zn(2+). The roles of the triad, cis-peptide, and metal ion in the catalysis are proposed. Because of extensive homology between PH999 and PZAase of M. tuberculosis (37% sequence identity), the structure of PH999 provides a structural basis for understanding PZA-resistance by M. tuberculosis harboring PZAase mutations.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21283666 S.Petrella, N.Gelus-Ziental, A.Maudry, C.Laurans, R.Boudjelloul, and W.Sougakoff (2011).
Crystal Structure of the Pyrazinamidase of Mycobacterium tuberculosis: Insights into Natural and Acquired Resistance to Pyrazinamide.
  PLoS One, 6, e15785.
PDB code: 3pl1
19932181 H.B.Luo, H.Zheng, M.D.Zimmerman, M.Chruszcz, T.Skarina, O.Egorova, A.Savchenko, A.M.Edwards, and W.Minor (2010).
Crystal structure and molecular modeling study of N-carbamoylsarcosine amidase Ta0454 from Thermoplasma acidophilum.
  J Struct Biol, 169, 304-311.
PDB code: 3eef
20727143 J.Jonmalung, T.Prammananan, M.Leechawengwongs, and A.Chaiprasert (2010).
Surveillance of pyrazinamide susceptibility among multidrug-resistant Mycobacterium tuberculosis isolates from Siriraj Hospital, Thailand.
  BMC Microbiol, 10, 223.  
20099871 K.M.McCulloch, T.Mukherjee, T.P.Begley, and S.E.Ealick (2010).
Structure determination and characterization of the vitamin B6 degradative enzyme (E)-2-(acetamidomethylene)succinate hydrolase.
  Biochemistry, 49, 1226-1235.
PDB code: 3kxp
19963078 M.Zimic, P.Sheen, M.Quiliano, A.Gutierrez, and R.H.Gilman (2010).
Peruvian and globally reported amino acid substitutions on the Mycobacterium tuberculosis pyrazinamidase suggest a conserved pattern of mutations associated to pyrazinamide resistance.
  Infect Genet Evol, 10, 346-349.  
19249243 P.Sheen, P.Ferrer, R.H.Gilman, J.López-Llano, P.Fuentes, E.Valencia, and M.J.Zimic (2009).
Effect of pyrazinamidase activity on pyrazinamide resistance in Mycobacterium tuberculosis.
  Tuberculosis (Edinb), 89, 109-113.  
19820182 T.L.Vrablik, L.Huang, S.E.Lange, and W.Hanna-Rose (2009).
Nicotinamidase modulation of NAD+ biosynthesis and nicotinamide levels separately affect reproductive development and cell survival in C. elegans.
  Development, 136, 3637-3646.  
18201201 H.Zhang, J.Y.Deng, L.J.Bi, Y.F.Zhou, Z.P.Zhang, C.G.Zhang, Y.Zhang, and X.E.Zhang (2008).
Characterization of Mycobacterium tuberculosis nicotinamidase/pyrazinamidase.
  FEBS J, 275, 753-762.  
18678916 J.I.Jiménez, A.Canales, J.Jiménez-Barbero, K.Ginalski, L.Rychlewski, J.L.García, and E.Díaz (2008).
Deciphering the genetic determinants for aerobic nicotinic acid degradation: the nic cluster from Pseudomonas putida KT2440.
  Proc Natl Acad Sci U S A, 105, 11329-11334.  
17657805 M.Babor, S.Gerzon, B.Raveh, V.Sobolev, and M.Edelman (2008).
Prediction of transition metal-binding sites from apo protein structures.
  Proteins, 70, 208-217.  
18678867 V.Balan, G.S.Miller, L.Kaplun, K.Balan, Z.Z.Chong, F.Li, A.Kaplun, M.F.Vanberkum, R.Arking, D.C.Freeman, K.Maiese, and G.Tzivion (2008).
Life span extension and neuronal cell protection by Drosophila nicotinamidase.
  J Biol Chem, 283, 27810-27819.  
17382284 G.Hu, A.B.Taylor, L.McAlister-Henn, and P.J.Hart (2007).
Crystal structure of the yeast nicotinamidase Pnc1p.
  Arch Biochem Biophys, 461, 66-75.
PDB code: 2h0r
14729974 C.M.Gallo, D.L.Smith, and J.S.Smith (2004).
Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity.
  Mol Cell Biol, 24, 1301-1312.  
12694619 J.E.Purser, M.B.Lawrenz, M.J.Caimano, J.K.Howell, J.D.Radolf, and S.J.Norris (2003).
A plasmid-encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host.
  Mol Microbiol, 48, 753-764.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.