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PDBsum entry 1nxk
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protein ligands Protein-protein interface(s) links
Transferase PDB id
1nxk

 

 

 

 

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Contents
Protein chains
290 a.a. *
306 a.a. *
Ligands
STU ×4
SO4 ×2
Waters ×42
* Residue conservation analysis
PDB id:
1nxk
Name: Transferase
Title: Crystal structure of staurosporine bound to map kap kinase 2
Structure: Map kinase-activated protein kinase 2. Chain: a, b, c, d. Fragment: mk2. Synonym: mapk-activated protein kinase 2, mapkap kinase 2, mapkapk-2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapkapk2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dodecamer (from PQS)
Resolution:
2.70Å     R-factor:   0.239     R-free:   0.274
Authors: K.W.Underwood,K.D.Parris,E.Federico,L.Mosyak,R.M.Czerwinski,T.Shane, M.Taylor,K.Svenson,Y.Liu,C.L.Hsiao,S.Wolfrom,K.Malakian,J.B.Telliez, L.L.Lin,R.W.Kriz,J.Seehra,W.S.Somers,M.L.Stahl
Key ref:
K.W.Underwood et al. (2003). Catalytically active MAP KAP kinase 2 structures in complex with staurosporine and ADP reveal differences with the autoinhibited enzyme. Structure, 11, 627-636. PubMed id: 12791252 DOI: 10.1016/S0969-2126(03)00092-3
Date:
10-Feb-03     Release date:   14-Oct-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P49137  (MAPK2_HUMAN) -  MAP kinase-activated protein kinase 2 from Homo sapiens
Seq:
Struc: 		400 a.a.
290 a.a.
Protein chain
P49137  (MAPK2_HUMAN) -  MAP kinase-activated protein kinase 2 from Homo sapiens
Seq:
Struc: 		400 a.a.
306 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.2.7.11.1  - non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      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+
L-seryl-[protein]
 + ATP
 = O-phospho-L-seryl-[protein]
 + ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(03)00092-3 Structure 11:627-636 (2003)
PubMed id: 12791252  
 
 
Catalytically active MAP KAP kinase 2 structures in complex with staurosporine and ADP reveal differences with the autoinhibited enzyme.
K.W.Underwood, K.D.Parris, E.Federico, L.Mosyak, R.M.Czerwinski, T.Shane, M.Taylor, K.Svenson, Y.Liu, C.L.Hsiao, S.Wolfrom, M.Maguire, K.Malakian, J.B.Telliez, L.L.Lin, R.W.Kriz, J.Seehra, W.S.Somers, M.L.Stahl.
 
  ABSTRACT  
 
MAP KAP kinase 2 (MK2), a Ser/Thr kinase, plays a crucial role in the inflammatory process. We have determined the crystal structures of a catalytically active C-terminal deletion form of human MK2, residues 41-364, in complex with staurosporine at 2.7 A and with ADP at 3.2 A, revealing overall structural similarity with other Ser/Thr kinases. Kinetic analysis reveals that the K(m) for ATP is very similar for MK2 41-364 and p38-activated MK2 41-400. Conversely, the catalytic rate and binding for peptide substrate are dramatically reduced in MK2 41-364. However, phosphorylation of MK2 41-364 by p38 restores the V(max) and K(m) for peptide substrate to values comparable to those seen in p38-activated MK2 41-400, suggesting a mechanism for regulation of enzyme activity.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Comparison of Ser/Thr KinasesRibbons representation of (A) MK2 41-364, (B) MK2 47-400 (Protein Data Bank ID 1KWP), (C) titan kinase (1TKI), (D) camp-dependent kinase (1ATP), and (E) Ca^2+/calmodulin-dependent kinase (1A06). Each structure is depicted in approximately the same orientation; autoinhibitory domain, red. The figures were generated with Ribbons (Carson, 1997).
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 627-636) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20640477 S.Kostenko, M.T.Khan, I.Sylte, and U.Moens (2011).
The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor.
  Cell Mol Life Sci, 68, 289-301.  
20057052 A.Fujino, K.Fukushima, N.Namiki, T.Kosugi, and M.Takimoto-Kamimura (2010).
Structural analysis of an MK2-inhibitor complex: insight into the regulation of the secondary structure of the Gly-rich loop by TEI-I01800.
  Acta Crystallogr D Biol Crystallogr, 66, 80-87.
PDB code: 3a2c
  19937655 R.Cheng, B.Felicetti, S.Palan, I.Toogood-Johnson, C.Scheich, J.Barker, M.Whittaker, and T.Hesterkamp (2010).
High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand.
  Protein Sci, 19, 168-173.
PDB code: 3fhr
19282986 B.A.Holloway, S.Gomez de la Torre Canny, Y.Ye, D.C.Slusarski, C.M.Freisinger, R.Dosch, M.M.Chou, D.S.Wagner, and M.C.Mullins (2009).
A novel role for MAPKAPK2 in morphogenesis during zebrafish development.
  PLoS Genet, 5, e1000413.  
19296855 M.A.Argiriadi, S.Sousa, D.Banach, D.Marcotte, T.Xiang, M.J.Tomlinson, M.Demers, C.Harris, S.Kwak, J.Hardman, M.Pietras, L.Quinn, J.DiMauro, B.Ni, J.Mankovich, D.W.Borhani, R.V.Talanian, and R.Sadhukhan (2009).
Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study.
  BMC Struct Biol, 9, 16.  
18184589 J.Eswaran, A.Bernad, J.M.Ligos, B.Guinea, J.E.Debreczeni, F.Sobott, S.A.Parker, R.Najmanovich, B.E.Turk, and S.Knapp (2008).
Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture.
  Structure, 16, 115-124.  
18620516 S.Duraisamy, M.Bajpai, U.Bughani, S.G.Dastidar, A.Ray, and P.Chopra (2008).
MK2: a novel molecular target for anti-inflammatory therapy.
  Expert Opin Ther Targets, 12, 921-936.  
17937911 G.Bunkoczi, E.Salah, P.Filippakopoulos, O.Fedorov, S.Müller, F.Sobott, S.A.Parker, H.Zhang, W.Min, B.E.Turk, and S.Knapp (2007).
Structural and functional characterization of the human protein kinase ASK1.
  Structure, 15, 1215-1226.
PDB code: 2clq
17500509 H.Al-Ali, T.J.Ragan, X.Gao, and T.K.Harris (2007).
Reconstitution of modular PDK1 functions on trans-splicing of the regulatory PH and catalytic kinase domains.
  Bioconjug Chem, 18, 1294-1302.  
17292828 H.C.Reinhardt, A.S.Aslanian, J.A.Lees, and M.B.Yaffe (2007).
p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage.
  Cancer Cell, 11, 175-189.  
17036304 C.S.Page, and P.A.Bates (2006).
Can MM-PBSA calculations predict the specificities of protein kinase inhibitors?
  J Comput Chem, 27, 1990-2007.  
17132859 G.A.Malawski, R.C.Hillig, F.Monteclaro, U.Eberspaecher, A.A.Schmitz, K.Crusius, M.Huber, U.Egner, P.Donner, and B.Müller-Tiemann (2006).
Identifying protein construct variants with increased crystallization propensity--a case study.
  Protein Sci, 15, 2718-2728.  
16421520 M.Gaestel (2006).
MAPKAP kinases - MKs - two's company, three's a crowd.
  Nat Rev Mol Cell Biol, 7, 120-130.  
15692053 C.McCormick, and D.Ganem (2005).
The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs.
  Science, 307, 739-741.  
15629715 I.A.Manke, A.Nguyen, D.Lim, M.Q.Stewart, A.E.Elia, and M.B.Yaffe (2005).
MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation.
  Mol Cell, 17, 37-48.  
15292186 L.Jin, S.Pluskey, E.C.Petrella, S.M.Cantin, J.C.Gorga, M.J.Rynkiewicz, P.Pandey, J.E.Strickler, R.E.Babine, D.T.Weaver, and K.J.Seidl (2004).
The three-dimensional structure of the ZAP-70 kinase domain in complex with staurosporine: implications for the design of selective inhibitors.
  J Biol Chem, 279, 42818-42825.
PDB code: 1u59
15538386 S.Schumacher, K.Laass, S.Kant, Y.Shi, A.Visel, A.D.Gruber, A.Kotlyarov, and M.Gaestel (2004).
Scaffolding by ERK3 regulates MK5 in development.
  EMBO J, 23, 4770-4779.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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