3K4V

New crystal form of HIV-1 Protease/Saquinavir structure reveals carbamylation of N-terminal proline

PDB DOI: https://doi.org/10.2210/pdb3K4V/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Human immunodeficiency virus type 1 BH10
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2009-10-06 Released: 2010-06-09
Deposition Author(s): Olajuyigbe, F.M., Demitri, N., Ajele, J.O., Maurizio, E., Randaccio, L., Geremia, S.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.39 ?
R-Value Free: 0.227
R-Value Observed: 0.159

Starting Model: experimental
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Ligand Structure Quality Assessment

This is version 1.6 of the entry. See complete history.

Literature

Carbamylation of N-terminal proline.

Olajuyigbe, F.M., Demitri, N., Ajele, J.O., Maurizio, E., Randaccio, L., Geremia, S.

(2010) ACS Med Chem Lett 1: 254-257

PubMed: 24900204 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/ml100046d
Primary Citation of Related Structures:
3K4V

PubMed Abstract:
Protein carbamylation is of great concern both in vivo and in vitro. Here, we report the first structural characterization of a protein carbamylated at the N-terminal proline. The unexpected carbamylation of the α-amino group of the least reactive codified amino acid has been detected in high-resolution electron density maps of a new crystal form of the HIV-1 protease/saquinavir complex. The carbamyl group is found coplanar to the proline ring with a trans conformation. The reaction of N-terminal with cyanate ion derived from the chaotropic agent urea was confirmed by mass spectra analysis on protease single crystals. Implications of carbamylation process in vitro and in vivo are discussed.

Organizational Affiliation

Department of Chemical Sciences ; Department of Biochemistry, Federal University of Technology, 340001 Akure, Nigeria.

Macromolecule Content

Total Structure Weight: 44.71 kDa
Atom Count: 3,547
Modelled Residue Count: 398
Deposited Residue Count: 398
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
HIV-1 Protease	A, B	100	Human immunodeficiency virus type 1 BH10	Mutation(s): 5 Gene Names: gag-pol EC: 3.4.23.16
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

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(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
HIV-1 Protease	C, D	99	Human immunodeficiency virus type 1 BH10	Mutation(s): 5 Gene Names: gag-pol EC: 3.4.23.16
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 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ROC Query on ROC Download Ideal Coordinates CCD File SDF format, chain G [auth B] SDF format, chain J [auth D] MOL2 format, chain G [auth B] MOL2 format, chain J [auth D] mmCIF format, chain G [auth B] mmCIF format, chain J [auth D]	G [auth B], J [auth D]	(2S)-N-[(2S,3R)-4-[(2S,3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1 -phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide C₃₈ H₅₀ N₆ O₅ QWAXKHKRTORLEM-UGJKXSETSA-N		Interactions Focus chain G [auth B] Focus chain J [auth D] Interactions & Density Focus chain G [auth B] Focus chain J [auth D]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain I [auth C] SDF format, chain K [auth D] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain I [auth C] MOL2 format, chain K [auth D] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain I [auth C] mmCIF format, chain K [auth D]	E [auth A], F [auth A], I [auth C], K [auth D]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain I [auth C] Focus chain K [auth D] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain I [auth C] Focus chain K [auth D]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain H [auth B] MOL2 format, chain H [auth B] mmCIF format, chain H [auth B]	H [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain H [auth B] Interactions & Density Focus chain H [auth B]

Biologically Interesting Molecules (External Reference) 1 Unique

Entity ID: 4
ID	Chains	Name	Type/Class	2D Diagram	3D Interactions
PRD_000454 (ROC) Query on PRD_000454	G [auth B], J [auth D]	Saquinavir	Peptide-like / Inhibitor		Interactions Focus chain G [auth B] Focus chain J [auth D] Interactions & Density Focus chain G [auth B] Focus chain J [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.39 ?
R-Value Free: 0.227
R-Value Observed: 0.159
Space Group: P 1 2₁ 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 51.205	α = 90
b = 62.673	β = 98.42
c = 59.076	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data collection
AMoRE	phasing
SHELXL-97	refinement
MOSFLM	data reduction
SCALA	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-06-09

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2010-06-09
Type: Initial release
Version 1.1: 2011-07-13
Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
Version 1.2: 2011-12-07
Changes: Database references
Version 1.3: 2012-12-12
Changes: Other
Version 1.4: 2014-09-24
Changes: Database references
Version 1.5: 2021-10-13
Changes: Database references, Derived calculations, Structure summary
Version 1.6: 2023-09-06
Changes: Data collection, Refinement description