spacer
spacer

PDBsum entry 4isf

Go to PDB code: 
protein ligands metals links
Transferase/transferase activator PDB id
4isf
Jmol
Contents
Protein chain
428 a.a.
Ligands
GLC
1FX
Metals
IOD
Waters ×245
PDB id:
4isf
Name: Transferase/transferase activator
Title: Human glucokinase in complex with novel activator (2s)-3-cyc (6-fluoro-2,4-dioxo-1,4-dihydroquinazolin-3(2h)-yl)-n-(1,3- yl)propanamide
Structure: Glucokinase. Chain: a. Fragment: unp residues 16-465. Synonym: hexokinase type iv, hk iv, hexokinase-4, hk4, hexo engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gck, hxk4 isoform ii. Expressed in: escherichia coli. Expression_system_taxid: 668369.
Resolution:
2.09Å     R-factor:   0.201     R-free:   0.258
Authors: D.Hosfield,R.J.Skene
Key ref: Z.S.Cheruvallath et al. (2013). Design, synthesis and SAR of novel glucokinase activators. Bioorg Med Chem Lett, 23, 2166-2171. PubMed id: 23434031 DOI: 10.1016/j.bmcl.2013.01.093
Date:
16-Jan-13     Release date:   20-Mar-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P35557  (HXK4_HUMAN) -  Glucokinase
Seq:
Struc:
465 a.a.
428 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.7.1.2  - Glucokinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + D-glucose = ADP + D-glucose 6-phosphate
ATP
+
D-glucose
Bound ligand (Het Group name = GLC)
corresponds exactly
= ADP
+ D-glucose 6-phosphate
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   35 terms 
  Biochemical function     catalytic activity     15 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2013.01.093 Bioorg Med Chem Lett 23:2166-2171 (2013)
PubMed id: 23434031  
 
 
Design, synthesis and SAR of novel glucokinase activators.
Z.S.Cheruvallath, S.L.Gwaltney, M.Sabat, M.Tang, J.Feng, H.Wang, J.Miura, P.Guntupalli, A.Jennings, D.Hosfield, B.Lee, Y.Wu.
 
  ABSTRACT  
 
Guided by co-crystal structures of compounds 15, 22 and 30, an SBDD approach led to the discovery of the 6-methyl pyridone series as a novel class of GKAs that potently activate GK in enzyme and cell assays. Anti-diabetic OGTT efficacy was demonstrated with 54 in a mouse model of type 2 diabetes.