PDBsum entry 3vqp

Transferase/transferase inhibitor

PDB id: 3vqp

Contents

Protein chains

141 a.a.

Ligands

SO4 ×2

DBJ

Metals

_CD ×4

_CL

Waters ×47

PDB id:

3vqp

Name:

Transferase/transferase inhibitor

Title:

HIV-1 in core domain in complex with 2,3-dihydro-1,4-benzodioxin-5- ylmethanol

Structure:

Pol polyprotein. Chain: a, b. Fragment: integrase core domain, unp residues 770-927. Engineered: yes. Mutation: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Strain: nl43. Gene: pol. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.199 R-free: 0.236

Authors:

J.Wielens,D.K.Chalmers,M.W.Parker,M.J.Scanlon

Key ref:

J.Wielens et al. (2013). Parallel screening of low molecular weight fragment libraries: do differences in methodology affect hit identification? J Biomol Screen, 18, 147-159. PubMed id: 23139382

Date:

29-Mar-12 Release date: 30-Jan-13

Protein chains

Q72498  (Q72498_HV1) -  POL polyprotein (Fragment) from Human immunodeficiency virus type 1

Seq: 1003 a.a.

Struc: 141 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.3.1.13.2 - exoribonuclease H.
• Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
• Enzyme class 2: E.C.3.1.26.13 - retroviral ribonuclease H.

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.

J Biomol Screen 18:147-159 (2013)

PubMed id: 23139382

Parallel screening of low molecular weight fragment libraries: do differences in methodology affect hit identification?

J.Wielens, S.J.Headey, D.I.Rhodes, R.J.Mulder, O.Dolezal, J.J.Deadman, J.Newman, D.K.Chalmers, M.W.Parker, T.S.Peat, M.J.Scanlon.

ABSTRACT

Fragment screening is becoming widely accepted as a technique to identify hit compounds for the development of novel lead compounds. In neighboring laboratories, we have recently, and independently, performed a fragment screening campaign on the HIV-1 integrase core domain (IN) using similar commercially purchased fragment libraries. The two campaigns used different screening methods for the preliminary identification of fragment hits; one used saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR), and the other used surface plasmon resonance (SPR) spectroscopy. Both initial screens were followed by X-ray crystallography. Using the STD-NMR/X-ray approach, 15 IN/fragment complexes were identified, whereas the SPR/X-ray approach found 6 complexes. In this article, we compare the approaches that were taken by each group and the results obtained, and we look at what factors could potentially influence the final results. We find that despite using different approaches with little overlap of initial hits, both approaches identified binding sites on IN that provided a basis for fragment-based lead discovery and further lead development. Comparison of hits identified in the two studies highlights a key role for both the conditions under which fragment binding is measured and the criteria selected to classify hits.