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PDBsum entry 4lc9

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protein ligands metals Protein-protein interface(s) links
Transferase/transferase regulator PDB id
4lc9
Jmol
Contents
Protein chains
567 a.a.
422 a.a.
Ligands
F6P
Metals
_NA
PDB id:
4lc9
Name: Transferase/transferase regulator
Title: Structural basis for regulation of human glucokinase by gluc regulatory protein
Structure: Glucokinase regulatory protein. Chain: a. Synonym: glucokinase regulator. Engineered: yes. Glucokinase. Chain: b. Synonym: hexokinase type iv, hk iv, hexokinase-4, hk4, hexo engineered: yes
Source: Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: gckr. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
3.40Å     R-factor:   0.246     R-free:   0.292
Authors: T.Beck,B.G.Miller
Key ref: T.Beck and B.G.Miller (2013). Structural basis for regulation of human glucokinase by glucokinase regulatory protein. Biochemistry, 52, 6232-6239. PubMed id: 23957911 DOI: 10.1021/bi400838t
Date:
21-Jun-13     Release date:   04-Sep-13    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q07071  (GCKR_RAT) -  Glucokinase regulatory protein
Seq:
Struc:
 
Seq:
Struc:
627 a.a.
567 a.a.
Protein chain
Pfam   ArchSchema ?
P35557  (HXK4_HUMAN) -  Glucokinase
Seq:
Struc:
465 a.a.
422 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain B: E.C.2.7.1.2  - Glucokinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + D-glucose = ADP + D-glucose 6-phosphate
ATP
+ D-glucose
= ADP
+
D-glucose 6-phosphate
Bound ligand (Het Group name = F6P)
corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   7 terms 
  Biological process     metabolic process   42 terms 
  Biochemical function     catalytic activity     20 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi400838t Biochemistry 52:6232-6239 (2013)
PubMed id: 23957911  
 
 
Structural basis for regulation of human glucokinase by glucokinase regulatory protein.
T.Beck, B.G.Miller.
 
  ABSTRACT  
 
Glucokinase (GCK) is responsible for maintaining glucose homeostasis in the human body. Dysfunction or misregulation of GCK causes hyperinsulinemia, hypertriglyceridemia, and type 2 diabetes. In the liver, GCK is regulated by interaction with the glucokinase regulatory protein (GKRP), a 68 kDa polypeptide that functions as a competitive inhibitor of glucose binding to GCK. Formation of the mammalian GCK-GKRP complex is stimulated by fructose 6-phosphate and antagonized by fructose 1-phosphate. Here we report the crystal structure of the mammalian GCK-GKRP complex in the presence of fructose 6-phosphate at a resolution of 3.50 Å. The interaction interface, which totals 2060 Å(2) of buried surface area, is characterized by a small number of polar contacts and substantial hydrophobic interactions. The structure of the complex reveals the molecular basis of disease states associated with impaired regulation of GCK by GKRP. It also offers insight into the modulation of complex stability by sugar phosphates. The atomic description of the mammalian GCK-GKRP complex provides a framework for the development of novel diabetes therapeutic agents that disrupt this critical macromolecular regulatory unit.