2pph

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{{STRUCTURE_2pph| PDB=2pph | SCENE= }}
{{STRUCTURE_2pph| PDB=2pph | SCENE= }}
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'''solution structure of human MEKK3 PB1 domain'''
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===solution structure of human MEKK3 PB1 domain===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_17985933}}
==About this Structure==
==About this Structure==
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2PPH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PPH OCA].
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2PPH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PPH OCA].
==Reference==
==Reference==
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[[Category: Zhang, J.]]
[[Category: Zhang, J.]]
[[Category: Kinase signaling domain]]
[[Category: Kinase signaling domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:37:42 2008''

Revision as of 13:37, 28 July 2008

Image:2pph.png

Template:STRUCTURE 2pph

solution structure of human MEKK3 PB1 domain

Template:ABSTRACT PUBMED 17985933

About this Structure

2PPH is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

Insight into the binding properties of MEKK3 PB1 to MEK5 PB1 from its solution structure., Hu Q, Shen W, Huang H, Liu J, Zhang J, Huang X, Wu J, Shi Y, Biochemistry. 2007 Nov 27;46(47):13478-89. Epub 2007 Nov 7. PMID:17985933

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