PDBsum entry 2geh

Lyase

PDB id

2geh

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Contents

			Protein chain

					257 a.a. *

			Ligands

					NHY

			Metals

					_ZN


					_HG ×2

			Waters ×176

* Residue conservation analysis

PDB id:

2geh

Links

Name:

Lyase

Title:

N-hydroxyurea, a versatile zinc binding function in the design of metalloenzyme inhibitors

Structure:

Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Ec: 4.2.1.1

Source:

Homo sapiens. Human. Organism_taxid: 9606

Resolution:

2.00Å

R-factor:

0.207

R-free:

0.229

Authors:

C.Temperini,A.Innocenti,A.Scozzafava,C.T.Supuran

Key ref:

C.Temperini et al. (2006). N-hydroxyurea--a versatile zinc binding function in the design of metalloenzyme inhibitors. Bioorg Med Chem Lett, 16, 4316-4320. PubMed id: 16759856 DOI: 10.1016/j.bmcl.2006.05.068

Date:

20-Mar-06

Release date:

20-Jun-06

PROCHECK

	Headers

	References

Protein chain

P00918 (CAH2_HUMAN) - Carbonic anhydrase 2 from Homo sapiens

Seq: Struc:					260 a.a. 257 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class 2:

E.C.4.2.1.1 - carbonic anhydrase.

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

Reaction:

hydrogencarbonate + H⁺ = CO2 + H2O

hydrogencarbonate	+	H(+)	=	CO2	+	H2O

Cofactor:

Zn(2+)

Enzyme class 3:

E.C.4.2.1.69 - cyanamide hydratase.

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

Reaction:

urea = cyanamide + H2O

urea
Bound ligand (Het Group name = NHY)
matches with 80.00% similarity

cyanamide

H2O

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1016/j.bmcl.2006.05.068	Bioorg Med Chem Lett 16:4316-4320 (2006)
PubMed id: 16759856

N-hydroxyurea--a versatile zinc binding function in the design of metalloenzyme inhibitors.
C.Temperini, A.Innocenti, A.Scozzafava, C.T.Supuran.

ABSTRACT

N-Hydroxyurea binds both to carbonic anhydrase (CA) and to matrix metalloproteinases (MMPs). X-ray crystallography showed N-hydroxyurea to bind in a bidentate mode by means of the oxygen and nitrogen atoms of the NHOH moiety to the Zn(II) ion of CA, participating in a network of hydrogen bonds with a water molecule and Thr199. A derivatized N-hydroxyurea showed low-micromolar affinity for several CAs. This simple zinc binding function may be exploited for obtaining potent metalloenzyme inhibitors, due to its versatility of binding to the metal ion present in the active site of such enzymes.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20629007

J.Schulze Wischeler, A.Innocenti, D.Vullo, A.Agrawal, S.M.Cohen, A.Heine, C.T.Supuran, and G.Klebe (2010).
Bidentate Zinc chelators for alpha-carbonic anhydrases that produce a trigonal bipyramidal coordination geometry.

ChemMedChem, 5, 1609-1615.

PDB code:

3m1k

19958583

N.Adhirajan, N.Shanmugasundaram, S.Shanmuganathan, and M.Babu (2009).
Collagen-based wound dressing for doxycycline delivery: in-vivo evaluation in an infected excisional wound model in rats.

J Pharm Pharmacol, 61, 1617-1623.

18335973

V.M.Krishnamurthy, G.K.Kaufman, A.R.Urbach, I.Gitlin, K.L.Gudiksen, D.B.Weibel, and G.M.Whitesides (2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.

Chem Rev, 108, 946.

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.