5CYQ

HIV-1 reverse transcriptase complexed with 4-bromopyrazole

PDB DOI: https://doi.org/10.2210/pdb5CYQ/pdb

Classification: TRANSFERASE
Organism(s): Human immunodeficiency virus type 1 BH10
Expression System: Escherichia coli BL21(DE3)
Mutation(s): Yes

Deposited: 2015-07-30 Released: 2015-12-30
Deposition Author(s): Bauman, J.D., Arnold, E.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.224
R-Value Work: 0.203
R-Value Observed: 0.204

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Rapid experimental SAD phasing and hot-spot identification with halogenated fragments.

Bauman, J.D., Harrison, J.J., Arnold, E.

(2016) IUCrJ 3: 51-60

PubMed: 26870381 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1107/S2052252515021259
Primary Citation of Related Structures:
5CXR, 5CYQ

PubMed Abstract:
Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a 'magic bullet' that is capable of binding at many of the ligand 'hot spots' found in HIV-1 reverse transcriptase (RT). The binding locations can be in pockets that are 'hidden' in the unliganded crystal form, allowing rapid identification of these sites for in silico screening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structures of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K) by single-wavelength anomalous dispersion (SAD) from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals.

Organizational Affiliation

Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University , 679 Hoes Lane, Piscataway, NJ 08854, USA.

Macromolecule Content

Total Structure Weight: 117.62 kDa
Atom Count: 8,420
Modelled Residue Count: 963
Deposited Residue Count: 985
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
HIV-1 reverse transcriptase, p66 subunit	A	557	Human immunodeficiency virus type 1 BH10	Mutation(s): 3 EC: 2.7.7.49
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10)) Explore P03366 Go to UniProtKB: P03366
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P03366
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
HIV-1 reverse transcriptase, p51 subunit	B	428	Human immunodeficiency virus type 1 BH10	Mutation(s): 1 EC: 2.7.7.49
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10)) Explore P03366 Go to UniProtKB: P03366
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P03366
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
T27 Query on T27 Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	4-{[4-({4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile C₂₂ H₁₈ N₆ YIBOMRUWOWDFLG-ONEGZZNKSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
BYZ Query on BYZ Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain S [auth B] SDF format, chain T [auth B] SDF format, chain U [auth B] SDF format, chain V [auth B] SDF format, chain W [auth B] SDF format, chain X [auth B] SDF format, chain Y [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] MOL2 format, chain V [auth B] MOL2 format, chain W [auth B] MOL2 format, chain X [auth B] MOL2 format, chain Y [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain S [auth B] mmCIF format, chain T [auth B] mmCIF format, chain U [auth B] mmCIF format, chain V [auth B] mmCIF format, chain W [auth B] mmCIF format, chain X [auth B] mmCIF format, chain Y [auth B]	D [auth A] E [auth A] F [auth A] G [auth A] H [auth A] D [auth A], E [auth A], F [auth A], G [auth A], H [auth A], I [auth A], J [auth A], K [auth A], S [auth B], T [auth B], U [auth B], V [auth B], W [auth B], X [auth B], Y [auth B]	4-bromo-1H-pyrazole C₃ H₃ Br N₂ WVGCPEDBFHEHEZ-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Focus chain Y [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Focus chain Y [auth B]
BR Query on BR Download Ideal Coordinates CCD File SDF format, chain P [auth A] SDF format, chain Q [auth A] SDF format, chain R [auth A] MOL2 format, chain P [auth A] MOL2 format, chain Q [auth A] MOL2 format, chain R [auth A] mmCIF format, chain P [auth A] mmCIF format, chain Q [auth A] mmCIF format, chain R [auth A]	P [auth A], Q [auth A], R [auth A]	BROMIDE ION Br CPELXLSAUQHCOX-UHFFFAOYSA-M		Interactions Focus chain P [auth A] Focus chain Q [auth A] Focus chain R [auth A] Interactions & Density Focus chain P [auth A] Focus chain Q [auth A] Focus chain R [auth A]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain AA [auth B] SDF format, chain BA [auth B] SDF format, chain CA [auth B] SDF format, chain DA [auth B] SDF format, chain EA [auth B] SDF format, chain L [auth A] SDF format, chain M [auth A] SDF format, chain N [auth A] SDF format, chain O [auth A] SDF format, chain Z [auth B] MOL2 format, chain AA [auth B] MOL2 format, chain BA [auth B] MOL2 format, chain CA [auth B] MOL2 format, chain DA [auth B] MOL2 format, chain EA [auth B] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain N [auth A] MOL2 format, chain O [auth A] MOL2 format, chain Z [auth B] mmCIF format, chain AA [auth B] mmCIF format, chain BA [auth B] mmCIF format, chain CA [auth B] mmCIF format, chain DA [auth B] mmCIF format, chain EA [auth B] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A] mmCIF format, chain N [auth A] mmCIF format, chain O [auth A] mmCIF format, chain Z [auth B]	AA [auth B] BA [auth B] CA [auth B] DA [auth B] EA [auth B] AA [auth B], BA [auth B], CA [auth B], DA [auth B], EA [auth B], L [auth A], M [auth A], N [auth A], O [auth A], Z [auth B]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain AA [auth B] Focus chain BA [auth B] Focus chain CA [auth B] Focus chain DA [auth B] Focus chain EA [auth B] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain Z [auth B] Interactions & Density Focus chain AA [auth B] Focus chain BA [auth B] Focus chain CA [auth B] Focus chain DA [auth B] Focus chain EA [auth B] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain Z [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
T27	BindingDB: 5CYQ	IC50: min: 0.68, max: 84 (nM) from 15 assay(s)
T27	BindingDB: 5CYQ	EC50: min: 0.2, max: 3.6 (nM) from 7 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.224
R-Value Work: 0.203
R-Value Observed: 0.204
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 161.887	α = 90
b = 73.167	β = 100.56
c = 108.894	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
DENZO	data reduction
SCALEPACK	data scaling
PHENIX	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2015-12-30

Deposition Author(s):

Bauman, J.D.

Arnold, E.

Revision History (Full details and data files)

Version 1.0: 2015-12-30
Type: Initial release
Version 1.1: 2018-04-18
Changes: Data collection, Database references, Derived calculations
Version 1.2: 2023-09-27
Changes: Data collection, Database references, Refinement description