PDBsum entry 2pph

Transferase

PDB id: 2pph

Contents

Protein chain

93 a.a. *

* Residue conservation analysis

PDB id:

2pph

Name:

Transferase

Title:

Solution structure of human mekk3 pb1 domain

Structure:

Mitogen-activated protein kinase kinase kinase 3. Chain: a. Fragment: pb1 domain (residues 42-126). Synonym: mapk/erk kinase kinase 3, mek kinase 3, mekk 3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mekk3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

Q.Hu,J.Zhang,J.Wu,Y.Shi

Key ref:

Q.Hu et al. (2007). Insight into the binding properties of MEKK3 PB1 to MEK5 PB1 from its solution structure. Biochemistry, 46, 13478-13489. PubMed id: 17985933

Date:

30-Apr-07 Release date: 22-May-07

Protein chain

Q99759  (M3K3_HUMAN) -  Mitogen-activated protein kinase kinase kinase 3 from Homo sapiens

Seq: 626 a.a.

Struc: 93 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.11.25 - mitogen-activated protein kinase kinase 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

Biochemistry 46:13478-13489 (2007)

PubMed id: 17985933

Insight into the binding properties of MEKK3 PB1 to MEK5 PB1 from its solution structure.

Q.Hu, W.Shen, H.Huang, J.Liu, J.Zhang, X.Huang, J.Wu, Y.Shi.

ABSTRACT

MEKK3 is a mitogen-activated protein kinase kinase kinase that participates in various signaling pathways. One of its functions is to activate the ERK5 signal pathway by phosphorylating and activating MEK5. MEKK3 and MEK5 each harbors a PB1 domain in the N-terminus, and they form a heterodimer via PB1-PB1 domain interaction that was reported to be indispensable to the activation of MEK5. Using NMR spectroscopy, we show here that a prolyl isomerization of the Gln38-Pro39 bond is present in MEKK3 PB1, which is the first case of structural heterogeneity within PB1 domains. We have solved the solution structures of both isomers and found a major difference between them in the Pro39 region. Residues Gly37-Leu40 form a type VIb beta-turn in the cis conformation, whereas no obvious character of beta-turn was observed in the trans conformation. Backbone dynamics studies have unraveled internal motions in the beta3/beta4-turn on a microsecond-millisecond time scale. Further investigation of its binding properties with MEK5 PB1 has demonstrated that MEKK3 PB1 binds MEK5 PB1 tightly with a Kd of about 10(-8) M. Mutagenesis analysis revealed that residues in the basic cluster of MEKK3 PB1 contributes differently to the PB1-PB1 interaction. Residues Lys 7 and Arg 5 play important roles in the interaction with MEK5 PB1. Taken together, this study provides new insights into structural details of MEKK3 PB1 and its binding properties with MEK5 PB1.