PDBsum entry 4riu

Lyase/lyase inhibitor

PDB id

4riu

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Contents

			Protein chain

					258 a.a.

			Ligands

					GOL ×3


					3QR

			Metals

					_ZN

			Waters ×202

PDB id:

4riu

Links

Name:

Lyase/lyase inhibitor

Title:

A carbonic anhydrase ix mimic in complex with a saccharin-based inhibitor

Structure:

Carbonic anhydrase 2. Chain: a. Synonym: carbonate dehydratase ii, carbonic anhydrasE C, cac, carbonic anhydrase ii, ca-ii. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.65Å

R-factor:

0.153

R-free:

0.176

Authors:

B.P.Mahon,R.Mckenna

Key ref:

B.P.Mahon et al. (2015). Saccharin: a lead compound for structure-based drug design of carbonic anhydrase IX inhibitors. Bioorg Med Chem Lett, 23, 849-854. PubMed id: 25614109 DOI: 10.1016/j.bmc.2014.12.030

Date:

07-Oct-14

Release date:

04-Feb-15

PROCHECK

	Headers

	References

Protein chain

P00918 (CAH2_HUMAN) - Carbonic anhydrase 2 from Homo sapiens

Seq: Struc:					260 a.a. 258 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.4.2.1.1 - carbonic anhydrase.

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

Reaction:

hydrogencarbonate + H⁺ = CO2 + H2O

hydrogencarbonate	+	H(+)	=	CO2	+	H2O

Cofactor:

Zn(2+)

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

Added reference

DOI no: 10.1016/j.bmc.2014.12.030	Bioorg Med Chem Lett 23:849-854 (2015)
PubMed id: 25614109

Saccharin: a lead compound for structure-based drug design of carbonic anhydrase IX inhibitors.
B.P.Mahon, A.M.Hendon, J.M.Driscoll, G.M.Rankin, S.A.Poulsen, C.T.Supuran, R.McKenna.

ABSTRACT

Carbonic anhydrase IX (CA IX) is a key modulator of aggressive tumor behavior and a prognostic marker and target for several cancers. Saccharin (SAC) based compounds may provide an avenue to overcome CA isoform specificity, as they display both nanomolar affinity and preferential binding, for CA IX compared to CA II (>50-fold for SAC and >1000-fold when SAC is conjugated to a carbohydrate moiety). The X-ray crystal structures of SAC and a SAC-carbohydrate conjugate bound to a CA IX-mimic are presented and compared to CA II. The structures provide substantial new insight into the mechanism of SAC selective CA isoform inhibition.