PDBsum entry 2fix

Hydrolase

PDB id

2fix

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Contents

			Protein chain

					319 a.a. *

			Ligands

					870 ×4

* Residue conservation analysis

PDB id:

2fix

Links

Name:

Hydrolase

Title:

Structure of human liver fbpase complexed with potent benzoxazole allosteric inhibitiors

Structure:

Fructose-1,6-bisphosphatase 1. Chain: a, d, h, l. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

3.50Å

R-factor:

0.252

R-free:

0.355

Authors:

C.Abad-Zapatero

Key ref:

C.Lai et al. (2006). Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg Med Chem Lett, 16, 1807-1810. PubMed id: 16446092 DOI: 10.1016/j.bmcl.2006.01.014

Date:

30-Dec-05

Release date:

21-Feb-06

PROCHECK

	Headers

	References

Protein chains

P09467 (F16P1_HUMAN) - Fructose-1,6-bisphosphatase 1 from Homo sapiens

Seq: Struc:					338 a.a. 319 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)



		Enzyme reactions

Enzyme class:

E.C.3.1.3.11 - fructose-bisphosphatase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

Pentose Phosphate Pathway (later stages)

Reaction:

beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-phosphate + phosphate

beta-D-fructose 1,6-bisphosphate	+	H2O	=	beta-D-fructose 6-phosphate	+	phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.bmcl.2006.01.014	Bioorg Med Chem Lett 16:1807-1810 (2006)
PubMed id: 16446092

Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase.
C.Lai, R.J.Gum, M.Daly, E.H.Fry, C.Hutchins, C.Abad-Zapatero, T.W.von Geldern.

ABSTRACT

A series of novel benzoxazole benzenesulfonamides was synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase-1). Extensive SAR studies led to a potent inhibitor, 53, with an IC(50) of 0.57microM. Compound 17 exhibited excellent bioavailability and a good pharmacokinetic profile in rats.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20577568

A.Rolfe, and P.R.Hanson (2009).
Microwave-assisted sequential one-pot protocol to benzothiadiazin-3-one-1,1-dioxides via a copper-catalyzed N-arylation strategy.

Tetrahedron Lett, 50, 6935-6937.

18855890

M.L.Mohler, Y.He, Z.Wu, D.J.Hwang, and D.D.Miller (2009).
Recent and emerging anti-diabetes targets.

Med Res Rev, 29, 125-195.

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