PDBsum entry 5fnh

Lyase

PDB id: 5fnh

Contents

Protein chain

257 a.a.

Ligands

GOL ×2

DMS

YIP ×2

Metals

_ZN

Waters ×253

PDB id:

5fnh

Name:

Lyase

Title:

Native state mass spectrometry, surface plasmon resonance and x-ray crystallography correlate strongly as a fragment screening combination

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

1.66Å R-factor: 0.139 R-free: 0.180

Authors:

L.A.Woods,O.Dolezal,B.Ren,J.H.Ryan,T.S.Peat,S.A.Poulsen

Key ref:

L.A.Woods et al. (2016). Native State Mass Spectrometry, Surface Plasmon Resonance, and X-ray Crystallography Correlate Strongly as a Fragment Screening Combination. J Med Chem, 59, 2192-2204. PubMed id: 26882437 DOI: 10.1021/acs.jmedchem.5b01940

Date:

15-Nov-15 Release date: 02-Mar-16

Protein chain

P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2 from Homo sapiens

Seq: 260 a.a.

Struc: 257 a.a.

Enzyme reactions

• Enzyme class 2: E.C.4.2.1.1 - carbonic anhydrase.
• Reaction: hydrogencarbonate + H⁺ = CO2 + H2O
• Cofactor: Zn(2+)
• Enzyme class 3: E.C.4.2.1.69 - cyanamide hydratase.
• Reaction: urea = 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: 10.1021/acs.jmedchem.5b01940

J Med Chem 59:2192-2204 (2016)

PubMed id: 26882437

Native State Mass Spectrometry, Surface Plasmon Resonance, and X-ray Crystallography Correlate Strongly as a Fragment Screening Combination.

L.A.Woods, O.Dolezal, B.Ren, J.H.Ryan, T.S.Peat, S.A.Poulsen.

ABSTRACT

Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.