PDBsum entry 1v7r

Hydrolase

PDB id: 1v7r

Contents

Protein chain

186 a.a. *

Ligands

CIT

Waters ×202

* Residue conservation analysis

PDB id:

1v7r

Name:

Hydrolase

Title:

Structure of nucleotide triphosphate pyrophosphatase from pyrococcus horikoshii ot3

Structure:

Hypothetical protein ph1917. Chain: a. Synonym: nucleotide triphosphate pyrophosphatase. Engineered: yes

Source:

Pyrococcus horikoshii. Organism_taxid: 70601. Strain: ot3. Gene: ntpase. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.40Å R-factor: 0.202 R-free: 0.223

Authors:

N.K.Lokanath,N.Kunishima,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

N.K.Lokanath et al. (2008). Structures of dimeric nonstandard nucleotide triphosphate pyrophosphatase from Pyrococcus horikoshii OT3: functional significance of interprotomer conformational changes. J Mol Biol, 375, 1013-1025. PubMed id: 18062990 DOI: 10.1016/j.jmb.2007.11.018

Date:

22-Dec-03 Release date: 30-Dec-03

Protein chain

O59580  (IXTPA_PYRHO) -  dITP/XTP pyrophosphatase from Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)

Seq: 186 a.a.

Struc: 186 a.a.

Enzyme reactions

• Enzyme class: E.C.3.6.1.66 - XTP/dITP diphosphatase.
• Reaction:
  1. XTP + H2O = XMP + diphosphate + H⁺
  2. dITP + H2O = dIMP + diphosphate + H⁺
  3. ITP + H2O = IMP + diphosphate + H⁺
• Cofactor: Mg(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.jmb.2007.11.018

J Mol Biol 375:1013-1025 (2008)

PubMed id: 18062990

Structures of dimeric nonstandard nucleotide triphosphate pyrophosphatase from Pyrococcus horikoshii OT3: functional significance of interprotomer conformational changes.

N.K.Lokanath, K.J.Pampa, K.Takio, N.Kunishima.

ABSTRACT

Nonstandard nucleotide triphosphate pyrophosphatase (NTPase) can efficiently hydrolyze nonstandard purine nucleotides in the presence of divalent cations. The crystal structures of the NTPase from Pyrococcus horikoshii OT3 (PhNTPase) have been determined in two unliganded forms and in three liganded forms with inosine 5'-monophosphate (IMP), ITP and Mn(2+), which visualize the recognition of these ligands unambiguously. The overall structure of PhNTPase is similar to that of previously reported crystal structures of the NTPase from Methanococcus jannaschii and the human ITPase. They share a similar protomer folding with two domains and a similar homodimeric quaternary structure. The dimeric interface of NTPase is well conserved, and the dimeric state might be important to constitute the active site of this enzyme. A conformational analysis of the five snapshots of PhNTPase structures using the multiple superposition method reveals that IMP, ITP and Mn(2+) bind to the active site without inducing large local conformational changes, indicating that a combination of interdomain and interprotomer rigid-body shifts mainly describes the conformational change of PhNTPase. The interdomain and interprotomer conformations of the ITP liganded form are essentially the same as those observed in the unliganded form 1, indicating that ITP binding to PhNTPase in solution may follow the selection mode in which ITP binds to the subunit that happens to be in the conformation observed in the unliganded form 1. In contrast to the human ITPase inducing a large domain closure upon ITP binding, the interdomain active site cleft is generally closed in PhNTPase and only the IMP binding form shows a remarkable domain opening by 14 degrees only in the B subunit. The interprotomer rigid-body rotation of PhNTPase has a tendency to keep the dimeric 2-fold symmetry, which is also true in human ITPase, thereby suggesting its relevance to the positive cooperativity of the dimeric NTPases. The exception of this rule is observed in the IMP liganded form in which the dimeric 2-fold symmetry is broken by a 3 degrees interprotomer rotation in an unusual direction. A combination of the exceptional interdomain and interprotomer relocations is most likely the reason for the observed asymmetric IMP binding that might be necessary for PhNTPase to release the reaction product IMP.

Selected figure(s)

Figure 3.
Fig. 3. Structural superposition of the PhNTPase protomer (magenta) with the MjNTPase (yellow) and human ITPase (green).

Figure 5.
Fig. 5. Recognition of ligands in PhNTPase. Flat representation of (a) IMP and (b) ITP binding sites. (c) Metal binding site. The polar interactions are denoted by dashed lines with distances in angstrom. Conserved residues and water molecules are labeled. (d) Molecular surface representation showing the IMP binding pocket.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 375, 1013-1025) copyright 2008.

Figures were selected by an automated process.