PDBsum entry 3l2b

Hydrolase

PDB id: 3l2b

Contents

Protein chains

233 a.a. *

Ligands

B4P

Waters ×74

* Residue conservation analysis

PDB id:

3l2b

Name:

Hydrolase

Title:

Crystal structure of the cbs and drtgg domains of the regulatory region of clostridium perfringens pyrophosphatase complexed with activator, diadenosine tetraphosphate

Structure:

Probable manganase-dependent inorganic pyrophosphatase. Chain: a, b. Fragment: regulatory region (unp residues 66-306). Engineered: yes

Source:

Clostridium perfringens. Organism_taxid: 195102. Strain: str. 13. Gene: cpe2055. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.27Å R-factor: 0.211 R-free: 0.259

Authors:

H.Tuominen,A.Salminen,E.Oksanen,J.Jamsen,O.Heikkila,L.Lehtio, N.N.Magretova,A.Goldman,A.A.Baykov,R.Lahti

Key ref:

H.Tuominen et al. (2010). Crystal structures of the CBS and DRTGG domains of the regulatory region of Clostridiumperfringens pyrophosphatase complexed with the inhibitor, AMP, and activator, diadenosine tetraphosphate. J Mol Biol, 398, 400-413. PubMed id: 20303981

Date:

15-Dec-09 Release date: 21-Apr-10

Protein chains

Q8XIQ9  (IPYR_CLOPE) -  Cobalt-dependent inorganic pyrophosphatase from Clostridium perfringens (strain 13 / Type A)

Seq: 549 a.a.

Struc: 233 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.6.1.1 - inorganic diphosphatase.
• Reaction: diphosphate + H2O = 2 phosphate + H⁺

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

Added reference

J Mol Biol 398:400-413 (2010)

PubMed id: 20303981

Crystal structures of the CBS and DRTGG domains of the regulatory region of Clostridiumperfringens pyrophosphatase complexed with the inhibitor, AMP, and activator, diadenosine tetraphosphate.

H.Tuominen, A.Salminen, E.Oksanen, J.Jämsen, O.Heikkilä, L.Lehtiö, N.N.Magretova, A.Goldman, A.A.Baykov, R.Lahti.

ABSTRACT

Nucleotide-binding cystathionine beta-synthase (CBS) domains serve as regulatory units in numerous proteins distributed in all kingdoms of life. However, the underlying regulatory mechanisms remain to be established. Recently, we described a subfamily of CBS domain-containing pyrophosphatases (PPases) within family II PPases. Here, we express a novel CBS-PPase from Clostridium perfringens (CPE2055) and show that the enzyme is inhibited by AMP and activated by a novel effector, diadenosine 5',5-P1,P4-tetraphosphate (AP(4)A). The structures of the AMP and AP(4)A complexes of the regulatory region of C. perfringens PPase (cpCBS), comprising a pair of CBS domains interlinked by a DRTGG domain, were determined at 2.3 A resolution using X-ray crystallography. The structures obtained are the first structures of a DRTGG domain as part of a larger protein structure. The AMP complex contains two AMP molecules per cpCBS dimer, each bound to a single monomer, whereas in the activator-bound complex, one AP(4)A molecule bridges two monomers. In the nucleotide-bound structures, activator binding induces significant opening of the CBS domain interface, compared with the inhibitor complex. These results provide structural insight into the mechanism of CBS-PPase regulation by nucleotides.