1WAK

X-ray structure of SRPK1

Summary for 1WAK

• Entry DOI: 10.2210/pdb1wak/pdb
• Related: 1WBP
• Descriptor: SERINE/THREONINE-PROTEIN KINASE SPRK1, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: srpk, kinase, serine/threonine-protein kinase, transferase, alternative splicing, atp-binding, chromosome partition, differentiation, mrna processing, mrna splicing, nuclear protein, nucleotide-binding, phosphorylation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: Q96SB4
• Total number of polymer chains: 1
• Total formula weight: 45535.94

Authors

Ngo, J.C.,Gullingsrud, J.,Chakrabarti, S.,Nolen, B.,Aubol, B.E.,Fu, X.D.,Adams, J.A.,Mccammon, J.A.,Ghosh, G. (deposition date: 2004-10-26, release date: 2006-07-11, Last modification date: 2024-05-08)

Primary citation

Ngo, J.C.,Gullingsrud, J.,Giang, K.,Yeh, M.J.,Fu, X.D.,Adams, J.A.,Mccammon, J.A.,Ghosh, G.
Sr Protein Kinase 1 is Resilient to Inactivation.
Structure, 15:123-, 2007

PubMed Abstract: SR protein kinase 1 (SRPK1) is a constitutively active kinase, which processively phosphorylates multiple serines within its substrates, ASF/SF2. We describe crystallographic, molecular dynamics, and biochemical results that shed light on how SRPK1 preserves its constitutive active conformation. Our structure reveals that unlike other known active kinase structures, the activation loop remains in an active state without any specific intraprotein interactions. Moreover, SRPK1 remains active despite extensive mutation to the activation segment. Molecular dynamics simulations reveal that SRPK1 partially absorbs the effect of mutations by forming compensatory interactions that maintain a catalytically competent chemical environment. Furthermore, SRPK1 is similarly resistant to deletion of its spacer loop region. Based upon a model of SRPK1 bound to a segment encompassing the docking motif and active-site peptide of ASF/SF2, we suggest a mechanism for processive phosphorylation and propose that the atypical resiliency we observed is critical for SRPK1's processive activity.

PubMed: 17223538
DOI: 10.1016/J.STR.2006.11.011

Experimental method

X-RAY DIFFRACTION (1.73 Å)