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Phosphotransferase PDB id
1pbw
Jmol
Contents
Protein chains
184 a.a. *
195 a.a. *
Waters ×267
* Residue conservation analysis
PDB id:
1pbw
Name: Phosphotransferase
Title: Structure of bcr-homology (bh) domain
Structure: Phosphatidylinositol 3-kinase. Chain: a, b. Fragment: p85 alpha subunit bcr-homology domain. Synonym: rhogap domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: t7-based expression system
Resolution:
2.00Å     R-factor:   0.184     R-free:   0.235
Authors: A.Musacchio,L.C.Cantley,S.C.Harrison
Key ref: A.Musacchio et al. (1996). Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit. Proc Natl Acad Sci U S A, 93, 14373-14378. PubMed id: 8962058 DOI: 10.1073/pnas.93.25.14373
Date:
17-Oct-96     Release date:   12-Mar-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P27986  (P85A_HUMAN) -  Phosphatidylinositol 3-kinase regulatory subunit alpha
Seq:
Struc: 		 
Seq:
Struc: 		724 a.a.
184 a.a.
Protein chain
Pfam   ArchSchema ?
P27986  (P85A_HUMAN) -  Phosphatidylinositol 3-kinase regulatory subunit alpha
Seq:
Struc: 		 
Seq:
Struc: 		724 a.a.
195 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   2 terms 
  Biological process     signal transduction   1 term 
  Biochemical function     phosphoinositide 3-kinase regulator activity     1 term  

 

 
DOI no: 10.1073/pnas.93.25.14373 Proc Natl Acad Sci U S A 93:14373-14378 (1996)
PubMed id: 8962058  
 
 
Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit.
A.Musacchio, L.C.Cantley, S.C.Harrison.
 
  ABSTRACT  
 
Proteins such as the product of the break-point cluster region, chimaerin, and the Src homology 3-binding protein 3BP1, are GTPase activating proteins (GAPs) for members of the Rho subfamily of small GTP-binding proteins (G proteins or GTPases). A 200-residue region, named the breakpoint cluster region-homology (BH) domain, is responsible for the GAP activity. We describe here the crystal structure of the BH domain from the p85 subunit of phosphatidylinositol 3-kinase at 2.0 A resolution. The domain is composed of seven helices, having a previously unobserved arrangement. A core of four helices contains most residues that are conserved in the BH family. Their packing suggests the location of a G-protein binding site. This structure of a GAP-like domain for small GTP-binding proteins provides a framework for analyzing the function of this class of molecules.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  19962457 S.B.Gabelli, D.Mandelker, O.Schmidt-Kittler, B.Vogelstein, and L.M.Amzel (2010).
Somatic mutations in PI3Kalpha: structural basis for enzyme activation and drug design.
  Biochim Biophys Acta, 1804, 533-540.  
19915146 H.Wu, S.C.Shekar, R.J.Flinn, M.El-Sibai, B.S.Jaiswal, K.I.Sen, V.Janakiraman, S.Seshagiri, G.J.Gerfen, M.E.Girvin, and J.M.Backer (2009).
Regulation of Class IA PI 3-kinases: C2 domain-iSH2 domain contacts inhibit p85/p110alpha and are disrupted in oncogenic p85 mutants.
  Proc Natl Acad Sci U S A, 106, 20258-20263.  
19321438 V.B.Kurella, J.M.Richard, C.L.Parke, L.F.Lecour, H.D.Bellamy, and D.K.Worthylake (2009).
Crystal structure of the GTPase-activating protein-related domain from IQGAP1.
  J Biol Chem, 284, 14857-14865.
PDB code: 3fay
19384426 A.Arcaro, and A.S.Guerreiro (2007).
The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications.
  Curr Genomics, 8, 271-306.  
17283057 C.M.Taniguchi, J.O.Aleman, K.Ueki, J.Luo, T.Asano, H.Kaneto, G.Stephanopoulos, L.C.Cantley, and C.R.Kahn (2007).
The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance.
  Mol Cell Biol, 27, 2830-2840.  
17008718 S.Reich, L.H.Puckey, C.L.Cheetham, R.Harris, A.A.Ali, U.Bhattacharyya, K.Maclagan, K.A.Powell, C.Prodromou, L.H.Pearl, P.C.Driscoll, and R.Savva (2006).
Combinatorial Domain Hunting: An effective approach for the identification of soluble protein domains adaptable to high-throughput applications.
  Protein Sci, 15, 2356-2365.  
  15209378 A.C.Donahue, and D.A.Fruman (2004).
PI3K signaling controls cell fate at many points in B lymphocyte development and activation.
  Semin Cell Dev Biol, 15, 183-197.  
15507211 B.Canagarajah, F.C.Leskow, J.Y.Ho, H.Mischak, L.F.Saidi, M.G.Kazanietz, and J.H.Hurley (2004).
Structural mechanism for lipid activation of the Rac-specific GAP, beta2-chimaerin.
  Cell, 119, 407-418.
PDB code: 1xa6
15302923 Z.J.Su, C.N.Hahn, G.J.Goodall, N.M.Reck, A.F.Leske, A.Davy, G.Kremmidiotis, M.A.Vadas, and J.R.Gamble (2004).
A vascular cell-restricted RhoGAP, p73RhoGAP, is a key regulator of angiogenesis.
  Proc Natl Acad Sci U S A, 101, 12212-12217.  
12618308 A.Bernards (2003).
GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila.
  Biochim Biophys Acta, 1603, 47-82.  
12145202 A.R.Marquitz, J.C.Harrison, I.Bose, T.R.Zyla, J.N.McMillan, and D.J.Lew (2002).
The Rho-GAP Bem2p plays a GAP-independent role in the morphogenesis checkpoint.
  EMBO J, 21, 4012-4025.  
12151228 S.Djordjevic, and P.C.Driscoll (2002).
Structural insight into substrate specificity and regulatory mechanisms of phosphoinositide 3-kinases.
  Trends Biochem Sci, 27, 426-432.  
10856234 H.Kang, C.Freund, J.S.Duke-Cohan, A.Musacchio, G.Wagner, and C.E.Rudd (2000).
SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55.
  EMBO J, 19, 2889-2899.  
10232922 P.J.Sheffield, U.Derewenda, J.Taylor, T.J.Parsons, and Z.S.Derewenda (1999).
Expression, purification and crystallization of a BH domain from the GTPase regulatory protein associated with focal adhesion kinase.
  Acta Crystallogr D Biol Crystallogr, 55, 356-359.  
10394366 R.C.Hillig, L.Renault, I.R.Vetter, T.Drell, A.Wittinghofer, and J.Becker (1999).
The crystal structure of rna1p: a new fold for a GTPase-activating protein.
  Mol Cell, 3, 781-791.
PDB code: 1yrg
9548756 B.Zhang, and Y.Zheng (1998).
Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190, p50RhoGAP, Bcr, and 3BP-1.
  Biochemistry, 37, 5249-5257.  
9759495 D.A.Fruman, R.E.Meyers, and L.C.Cantley (1998).
Phosphoinositide kinases.
  Annu Rev Biochem, 67, 481-507.  
9546212 E.F.Pai (1998).
The alpha and beta of turning on a molecular switch.
  Nat Struct Biol, 5, 259-263.  
9697416 K.Scheffzek, M.R.Ahmadian, and A.Wittinghofer (1998).
GTPase-activating proteins: helping hands to complement an active site.
  Trends Biochem Sci, 23, 257-262.  
9631293 S.J.Gamblin, and S.J.Smerdon (1998).
GTPase-activating proteins and their complexes.
  Curr Opin Struct Biol, 8, 195-201.  
9434896 M.Geyer, and A.Wittinghofer (1997).
GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins.
  Curr Opin Struct Biol, 7, 786-792.  
  9348541 R.T.Müller, U.Honnert, J.Reinhard, and M.Bähler (1997).
The rat myosin myr 5 is a GTPase-activating protein for Rho in vivo: essential role of arginine 1695.
  Mol Biol Cell, 8, 2039-2053.  
9242920 S.R.Sprang (1997).
G protein mechanisms: insights from structural analysis.
  Annu Rev Biochem, 66, 639-678.  
9434906 S.R.Sprang (1997).
G proteins, effectors and GAPs: structure and mechanism.
  Curr Opin Struct Biol, 7, 849-856.  
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.