PDBsum entry 3ddc

Hydrolase/apoptosis

PDB id: 3ddc

Contents

Protein chains

166 a.a. *

133 a.a. *

Ligands

GNP

Metals

_MG

Waters ×115

* Residue conservation analysis

PDB id:

3ddc

Name:

Hydrolase/apoptosis

Title:

Crystal structure of nore1a in complex with ras

Structure:

Gtpase hras. Chain: a. Fragment: unp residues 1-166. Synonym: transforming protein p21, p21ras, h-ras-1, c-h-ras, ha-ras. Engineered: yes. Mutation: yes. Ras association domain-containing family protein 5. Chain: b. Fragment: ras binding domain, unp residues 200-358.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hras, hras1. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. Mouse. Organism_taxid: 10090.

Resolution:

1.80Å R-factor: 0.195 R-free: 0.230

Authors:

B.Stieglitz,C.Bee,D.Schwarz,O.Yildiz,A.Moshnikova,A.Khokhlatchev, C.Herrmann

Key ref:

B.Stieglitz et al. (2008). Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II. Embo J, 27, 1995-2005. PubMed id: 18596699 DOI: 10.1038/emboj.2008.125

Date:

05-Jun-08 Release date: 15-Jul-08

Protein chain

P01112  (RASH_HUMAN) -  GTPase HRas from Homo sapiens

Seq: 189 a.a.

Struc: 166 a.a.*

Protein chain

Q5EBH1  (RASF5_MOUSE) -  Ras association domain-containing protein 5 from Mus musculus

Seq: 413 a.a.

Struc: 133 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain A: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP + H2O = GDP (Bound ligand (Het Group name = GNP) matches with 81.82% similarity) + phosphate + H(+)

• Enzyme class 2: Chain B: E.C.?

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

DOI no: 10.1038/emboj.2008.125

Embo J 27:1995-2005 (2008)

PubMed id: 18596699

Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II.

B.Stieglitz, C.Bee, D.Schwarz, O.Yildiz, A.Moshnikova, A.Khokhlatchev, C.Herrmann.

ABSTRACT

A class of putative Ras effectors called Ras association domain family (RASSF) represents non-enzymatic adaptors that were shown to be important in tumour suppression. RASSF5, a member of this family, exists in two splice variants known as NORE1A and RAPL. Both of them are involved in distinct cellular pathways triggered by Ras and Rap, respectively. Here we describe the crystal structure of Ras in complex with the Ras binding domain (RBD) of NORE1A/RAPL. All Ras effectors share a common topology in their RBD creating an interface with the switch I region of Ras, whereas NORE1A/RAPL RBD reveals additional structural elements forming a unique Ras switch II binding site. Consequently, the contact area of NORE1A is extended as compared with other Ras effectors. We demonstrate that the enlarged interface provides a rationale for an exceptionally long lifetime of the complex. This is a specific attribute characterizing the effector function of NORE1A/RAPL as adaptors, in contrast to classical enzymatic effectors such as Raf, RalGDS or PI3K, which are known to form highly dynamic short-lived complexes with Ras.