PDBsum entry 3ism

Hydrolase inhibitor/hydrolase

PDB id: 3ism

Contents

Protein chains

245 a.a. *

286 a.a. *

Ligands

TRS

Metals

_MG ×2

Waters ×328

* Residue conservation analysis

PDB id:

3ism

Name:

Hydrolase inhibitor/hydrolase

Title:

Crystal structure of the endog/endogi complex: mechanism of endog inhibition

Structure:

Cg8862. Chain: a, b. Fragment: unp residues 56-310. Synonym: endonuclease g, endog, ld35517p. Engineered: yes. Cg4930. Chain: c. Synonym: endogi, sd16985p. Engineered: yes.

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: cg8862, dmel_cg8862, endog. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: endogi, bg:ds07473.2, cg4930, dmel_cg4930.

Resolution:

2.20Å R-factor: 0.186 R-free: 0.223

Authors:

B.Loll,M.Gebhardt,E.Wahle,A.Meinhart

Key ref:

B.Loll et al. (2009). Crystal structure of the EndoG/EndoGI complex: mechanism of EndoG inhibition. Nucleic Acids Res, 37, 7312-7320. PubMed id: 19783821

Date:

26-Aug-09 Release date: 08-Sep-09

Protein chains

Q7JXB9  (Q7JXB9_DROME) -  Endonuclease from Drosophila melanogaster

Seq: 310 a.a.

Struc: 245 a.a.

Protein chain

Q9V3V9  (Q9V3V9_DROME) -  Endonuclease G inhibitor, isoform A from Drosophila melanogaster

Seq: 359 a.a.

Struc: 286 a.a.

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.3.1.30.- - ?????
• Enzyme class 2: Chain C: E.C.3.6.1.3 - Deleted entry.
• Reaction: ATP + H₂O = ADP + phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

Nucleic Acids Res 37:7312-7320 (2009)

PubMed id: 19783821

Crystal structure of the EndoG/EndoGI complex: mechanism of EndoG inhibition.

B.Loll, M.Gebhardt, E.Wahle, A.Meinhart.

ABSTRACT

EndoG is a ubiquitous nuclease that is translocated into the nucleus during apoptosis to participate in DNA degradation. The enzyme cleaves double- and single-stranded DNA and RNA. Related nucleases are found in eukaryotes and prokaryotes, which have evolved sophisticated mechanisms for genome protection against self-antagonizing nuclease activity. Common mechanisms of inhibition are secretion, sequestration into a separate cellular compartment or by binding to protein inhibitors. Although EndoG is silenced by compartmentalization into the mitochondrial intermembrane space, a nucleus-localized protein inhibitor protects cellular polynucleotides from degradation by stray EndoG under non-apoptotic conditions in Drosophila. Here, we report the first three-dimensional structure of EndoG in complex with its inhibitor EndoGI. Although the mechanism of inhibition is reminiscent of bacterial protein inhibitors, EndoGI has evolved independently from a generic protein-protein interaction module. EndoGI is a two-domain protein that binds the active sites of two monomers of EndoG, with EndoG being sandwiched between EndoGI. Since the amino acid sequences of eukaryotic EndoG homologues are highly conserved, this model is valid for eukaryotic dimeric EndoG in general. The structure indicates that the two active sites of EndoG occupy the most remote spatial position possible at the molecular surface and a concerted substrate processing is unlikely.