3QHW

Structure of a pCDK2/CyclinA transition-state mimic

Summary for 3QHW

• Entry DOI: 10.2210/pdb3qhw/pdb
• Related: 3QHR
• Descriptor: Cell division protein kinase 2, Cyclin-A2, CDK2 substrate peptide: PKTPKKAKKL, ... (9 entities in total)
• Functional Keywords: kinase catalytic domain, protein kinase, cyclin, phosphorylated thr-160, phosphorylated on thr-160, transferase-protein binding complex, transferase/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P51943
• Total number of polymer chains: 8
• Total formula weight: 133702.89

Authors

Young, M.A.,Jacobsen, D.M.,Bao, Z.Q. (deposition date: 2011-01-26, release date: 2011-05-25, Last modification date: 2024-10-16)

Primary citation

Bao, Z.Q.,Jacobsen, D.M.,Young, M.A.
Briefly Bound to Activate: Transient Binding of a Second Catalytic Magnesium Activates the Structure and Dynamics of CDK2 Kinase for Catalysis.
Structure, 19:675-690, 2011

PubMed Abstract: We have determined high-resolution crystal structures of a CDK2/Cyclin A transition state complex bound to ADP, substrate peptide, and MgF(3)(-). Compared to previous structures of active CDK2, the catalytic subunit of the kinase adopts a more closed conformation around the active site and now allows observation of a second Mg(2+) ion in the active site. Coupled with a strong [Mg(2+)] effect on in vitro kinase activity, the structures suggest that the transient binding of the second Mg(2+) ion is necessary to achieve maximum rate enhancement of the chemical reaction, and Mg(2+) concentration could represent an important regulator of CDK2 activity in vivo. Molecular dynamics simulations illustrate how the simultaneous binding of substrate peptide, ATP, and two Mg(2+) ions is able to induce a more rigid and closed organization of the active site that functions to orient the phosphates, stabilize the buildup of negative charge, and shield the subsequently activated γ-phosphate from solvent.

PubMed: 21565702
DOI: 10.1016/j.str.2011.02.016

Experimental method

X-RAY DIFFRACTION (1.91 Å)