4K4R
TL-3 inhibited Trp6Ala HIV Protease with 1-bromo-2-napthoic acid bound in exosite
Summary for 4K4R
| Entry DOI | 10.2210/pdb4k4r/pdb |
| Related | 4K4P 4K4Q |
| Related PRD ID | PRD_000434 |
| Descriptor | Gag-Pol polyprotein, DIMETHYL SULFOXIDE, 1-bromonaphthalene-2-carboxylic acid, ... (7 entities in total) |
| Functional Keywords | fragment binding, exosite, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Human immunodeficiency virus type 1 (HIV-1) |
| Cellular location | Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P12499 |
| Total number of polymer chains | 2 |
| Total formula weight | 23312.69 |
| Authors | Tiefenbrunn, T.,Stout, C.D. (deposition date: 2013-04-12, release date: 2013-09-18, Last modification date: 2024-02-28) |
| Primary citation | Tiefenbrunn, T.,Forli, S.,Happer, M.,Gonzalez, A.,Tsai, Y.,Soltis, M.,Elder, J.H.,Olson, A.J.,Stout, C.D. Crystallographic Fragment-Based Drug Discovery: Use of a Brominated Fragment Library Targeting HIV Protease. Chem.Biol.Drug Des., 83:141-148, 2014 Cited by PubMed Abstract: A library of 68 brominated fragments was screened against a new crystal form of inhibited HIV-1 protease in order to probe surface sites in soaking experiments. Often, fragments are weak binders with partial occupancy, resulting in weak, difficult-to-fit electron density. The use of a brominated fragment library addresses this challenge, as bromine can be located unequivocally via anomalous scattering. Data collection was carried out in an automated fashion using AutoDrug at SSRL. Novel hits were identified in the known surface sites: 3-bromo-2,6-dimethoxybenzoic acid (Br6) in the flap site and 1-bromo-2-naphthoic acid (Br27) in the exosite, expanding the chemistry of known fragments for development of higher affinity potential allosteric inhibitors. At the same time, mapping the binding sites of a number of weaker binding Br-fragments provides further insight into the nature of these surface pockets. PubMed: 23998903DOI: 10.1111/cbdd.12227 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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