1NH0

1.03 A structure of HIV-1 protease: inhibitor binding inside and outside the active site

PDB DOI: https://doi.org/10.2210/pdb1NH0/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Human immunodeficiency virus 1
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2002-12-18 Released: 2004-04-13
Deposition Author(s): Brynda, J., Rezacova, P., Fabry, M., Horejsi, M., Hradilek, M., Soucek, M., Konvalinka, J., Sedlacek, J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.03 Å
R-Value Free: 0.165
R-Value Work: 0.130
R-Value Observed: 0.131

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

This is version 1.4 of the entry. See complete history.

Literature

A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation, and Subsite-Pocket Interactions Analyzed at Atomic Resolution

Brynda, J., Rezacova, P., Fabry, M., Horejsi, M., Stouracova, R., Sedlacek, J., Soucek, M., Hradilek, M., Lepsik, M., Konvalinka, J.

(2004) J Med Chem 47: 2030-2036

PubMed: 15056001 Search on PubMed
DOI: https://doi.org/10.1021/jm031105q
Primary Citation of Related Structures:
1NH0

PubMed Abstract:
The X-ray structure of a complex of HIV-1 protease (PR) with a phenylnorstatine inhibitor Z-Pns-Phe-Glu-Glu-NH(2) has been determined at 1.03 A, the highest resolution so far reported for any HIV PR complex. The inhibitor shows subnanomolar K(i) values for both the wild-type PR and the variant representing one of the most common mutations linked to resistance development. The structure comprising the phenylnorstatine moiety of (2R,3S)-chirality displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. This high resolution makes it possible to assess the donor and acceptor relations of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. A structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses.

Organizational Affiliation

Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16637 Prague 6, Czech Republic. [email protected]

Macromolecule Content

Total Structure Weight: 23.42 kDa
Atom Count: 1,937
Modelled Residue Count: 208
Deposited Residue Count: 208
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
PROTEASE RETROPEPSIN	A, B	99	Human immunodeficiency virus 1	Mutation(s): 0 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

Find similar proteins by: Sequence | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
peptidomimetic inhibitor KI2-PHE-GLU-GLU-NH2	C [auth I], D [auth J]	5	N/A	Mutation(s): 0
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth B] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] mmCIF format, chain E [auth A] mmCIF format, chain G [auth B]	E [auth A], G [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain E [auth A] Focus chain G [auth B] Interactions & Density Focus chain E [auth A] Focus chain G [auth B]
BME Query on BME Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain H [auth B] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] mmCIF format, chain F [auth A] mmCIF format, chain H [auth B]	F [auth A], H [auth B]	BETA-MERCAPTOETHANOL C₂ H₆ O S DGVVWUTYPXICAM-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain H [auth B] Interactions & Density Focus chain F [auth A] Focus chain H [auth B]

Biologically Interesting Molecules (External Reference) 1 Unique

Entity ID: 2
ID	Chains	Name	Type/Class	2D Diagram	3D Interactions
PRD_000401 Query on PRD_000401	C [auth I], D [auth J]	PEPTIDOMIMETIC INHIBITOR KI2-PHE-GLU-GLU-NH2	Peptide-like / Inhibitor		Interactions Focus chain C [auth I] Focus chain D [auth J] Interactions & Density Focus chain C [auth I] Focus chain D [auth J]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.03 Å
R-Value Free: 0.165
R-Value Work: 0.130
R-Value Observed: 0.131
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 28.913	α = 90
b = 66.562	β = 90
c = 93.147	γ = 90

Software Package:

Software Name	Purpose
XDS	data scaling
XSCALE	data scaling
EPMR	phasing
SHELXL-97	refinement
XDS	data reduction

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2004-04-13

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2004-04-13
Type: Initial release
Version 1.1: 2008-04-29
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
Version 1.3: 2012-12-12
Changes: Other
Version 1.4: 2023-08-16
Changes: Data collection, Database references, Derived calculations, Refinement description