4FE6

Crystal Structure of HIV-1 Protease in Complex with an enamino-oxindole inhibitor

PDB DOI: https://doi.org/10.2210/pdb4FE6/pdb

Classification: HYDROLASE/INHIBITOR
Organism(s): Human immunodeficiency virus type 1 (BRU ISOLATE)
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2012-05-29 Released: 2012-07-18
Deposition Author(s): Silva, A.M., Eissenstat, M., Guerassina, T., Gulnik, S., Afonina, E., Yu, B., Erickson, J., Ludke, D., Yokoe, H.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.261
R-Value Work: 0.180
R-Value Observed: 0.184

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Enamino-oxindole HIV protease inhibitors.

Eissenstat, M., Guerassina, T., Gulnik, S., Afonina, E., Silva, A.M., Ludtke, D., Yokoe, H., Yu, B., Erickson, J.

(2012) Bioorg Med Chem Lett 22: 5078-5083

PubMed: 22749283 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2012.05.120
Primary Citation of Related Structures:
4FE6

PubMed Abstract:
We have designed and synthesized a series of HIV protease inhibitors (PIs) with enamino-oxindole substituents optimized to interact with the S2' subsite of the HIV protease binding pocket. Several of these inhibitors have sub-nanomolar K(i) and antiviral IC(50) in the low nM range against WT HIV and against a panel of multi-drug resistant (MDR) strains.

Organizational Affiliation

Sequoia Pharmaceuticals, Inc., Gaithersburg, MD 10878, USA. eissenst@comcast.net

Macromolecule Content

Total Structure Weight: 11.45 kDa
Atom Count: 896
Modelled Residue Count: 99
Deposited Residue Count: 99
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
HIV protease	A	99	Human immunodeficiency virus type 1 (BRU ISOLATE)	Mutation(s): 0 Gene Names: gag-pol EC: 3.4.23.16
UniProt
Find proteins for P03367 (Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI)) Explore P03367 Go to UniProtKB: P03367
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P03367
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
0TQ Query on 0TQ Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl {(2S,3R)-3-hydroxy-4-[({(3Z)-3-[1-(methylamino)ethylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl}sulfonyl)(2-methylpropyl)amino]-1-phenylbutan-2-yl}carbamate C₃₂ H₄₂ N₄ O₈ S CJXWCYBPIXFWOP-PEXZKGFOSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
0TQ	Binding MOAD: 4FE6	Ki: 0.1 (nM) from 1 assay(s)
0TQ	PDBBind: 4FE6	Ki: 0.1 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.261
R-Value Work: 0.180
R-Value Observed: 0.184
Space Group: P 6₁ 2 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 62.654	α = 90
b = 62.654	β = 90
c = 82.361	γ = 120

Software Package:

Software Name	Purpose
SCALEPACK	data scaling
REFMAC	refinement
PDB_EXTRACT	data extraction
StructureStudio	data collection
DENZO	data reduction

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-07-18

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2012-07-18
Type: Initial release
Version 1.1: 2012-08-01
Changes: Database references
Version 1.2: 2024-02-28
Changes: Data collection, Database references, Derived calculations