PDBsum entry 1far

Serine/threonine protein kinase

PDB id: 1far

Contents

Protein chain

52 a.a. *

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

1far

Name:

Serine/threonine protein kinase

Title:

Raf-1 cysteine rich domain, nmr, minimized average structure

Structure:

Raf-1. Chain: a. Fragment: cysteine-rich domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

1 models

Authors:

H.R.Mott,S.L.Campbell

Key ref:

H.R.Mott et al. (1996). The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site. Proc Natl Acad Sci U S A, 93, 8312-8317. PubMed id: 8710867

Date:

05-Sep-96 Release date: 27-Jan-97

Protein chain

P04049  (RAF1_HUMAN) -  RAF proto-oncogene serine/threonine-protein kinase from Homo sapiens

Seq: 648 a.a.

Struc: 52 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

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

reference

Proc Natl Acad Sci U S A 93:8312-8317 (1996)

PubMed id: 8710867

The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site.

H.R.Mott, J.W.Carpenter, S.Zhong, S.Ghosh, R.M.Bell, S.L.Campbell.

ABSTRACT

The Raf-1 protein kinase is the best-characterized downstream effector of activated Ras. Interaction with Ras leads to Raf-1 activation and results in transduction of cell growth and differentiation signals. The details of Raf-1 activation are unclear, but our characterization of a second Ras-binding site in the cysteine-rich domain (CRD) and the involvement of both Ras-binding sites in effective Raf-1-mediated transformation provides insight into the molecular aspects and consequences of Ras-Raf interactions. The Raf-1 CRD is a member of an emerging family of domains, many of which are found within signal transducing proteins. Several contain binding sites for diacylglycerol (or phorbol esters) and phosphatidylserine and are believed to play a role in membrane translocation and enzyme activation. The CRD from Raf-1 does not bind diacylglycerol but interacts with Ras and phosphatidylserine. To investigate the ligand-binding specificities associated with CRDs, we have determined the solution structure of the Raf-1 CRD using heteronuclear multidimensional NMR. We show that there are differences between this structure and the structures of two related domains from protein kinase C (PKC). The differences are confined to regions of the CRDs involved in binding phorbol ester in the PKC domains. Since phosphatidylserine is a common ligand, we expect its binding site to be located in regions where the structures of the Raf-1 and PKC domains are similar. The structure of the Raf-1 CRD represents an example of this family of domains that does not bind diacylglycerol and provides a framework for investigating its interactions with other molecules.