1NZQ

D-Phe-Pro-Arg-Type Thrombin Inhibitor

PDB DOI: https://doi.org/10.2210/pdb1NZQ/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2003-02-19 Released: 2003-10-14
Deposition Author(s): Lange, U.E., Bauke, D., Hornberger, W., Mack, H., Seitz, W., Hoeffken, H.W.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.18 Å
R-Value Free: 0.242
R-Value Work: 0.197
R-Value Observed: 0.197

wwPDB Validation 3D Report Full Report

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

Literature

D-Phe-Pro-Arg type thrombin inhibitors: unexpected selectivity by modification of the P1 moiety

Lange, U.E., Bauke, D., Hornberger, W., Mack, H., Seitz, W., Hoeffken, H.W.

(2003) Bioorg Med Chem Lett 13: 2029-2033

PubMed: 12781189 Search on PubMed
DOI: https://doi.org/10.1016/s0960-894x(03)00347-0
Primary Citation of Related Structures:
1NZQ, 1O0D

PubMed Abstract:
Synthesis of thrombin inhibitors and their binding mode to thrombin is described. Modification of the P1 moiety leads to an increased selectivity versus trypsin. The observed selectivity is discussed in view of their thrombin-inhibitor complex X-ray structures.

Organizational Affiliation

BASF AG, D-67056, Ludwigshafen, Germany. wolfgang.hoeffken@basf-ag.de

Macromolecule Content

Total Structure Weight: 35.85 kDa
Atom Count: 2,535
Modelled Residue Count: 289
Deposited Residue Count: 306
Unique protein chains: 3

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Thrombin light chain	A [auth L]	36	Homo sapiens	Mutation(s): 0 Gene Names: F2 EC: 3.4.21.5
UniProt & NIH Common Fund Data Resources
Find proteins for P00734 (Homo sapiens) Explore P00734 Go to UniProtKB: P00734
PHAROS: P00734 GTEx: ENSG00000180210
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00734
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Thrombin heavy chain	B [auth H]	259	Homo sapiens	Mutation(s): 0 Gene Names: F2 EC: 3.4.21.5
UniProt & NIH Common Fund Data Resources
Find proteins for P00734 (Homo sapiens) Explore P00734 Go to UniProtKB: P00734
PHAROS: P00734 GTEx: ENSG00000180210
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00734
Sequence Annotations Expand
Reference Sequence

Find similar proteins by: Sequence | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Decapeptide Hirudin Analogue	C [auth D]	11	N/A	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
162 Query on 162 Download Ideal Coordinates CCD File SDF format, chain D [auth H] MOL2 format, chain D [auth H]	D [auth H]	(2-{2-[(5-CARBAMIMIDOYL-1-METHYL-1H-PYRROL-3-YLMETHYL)-CARBAMOYL]-PYRROL-1-YL} -1-CYCLOHEXYLMETHYL-2-OXO-ETHYLAMINO)-ACETIC ACID C₂₃ H₃₂ N₆ O₄ NWTFRWIXCVUIDS-QGZVFWFLSA-N		Interactions Focus chain D [auth H]

Modified Residues 3 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
ALC Query on ALC	C [auth D]	L-PEPTIDE LINKING	C₉ H₁₇ N O₂		ALA
HYP Query on HYP	C [auth D]	L-PEPTIDE LINKING	C₅ H₉ N O₃		PRO
SMF Query on SMF	C [auth D]	L-PEPTIDE LINKING	C₁₀ H₁₃ N O₅ S		PHE

Binding Affinity Annotations
ID	Source	Binding Affinity
162	Binding MOAD: 1NZQ	IC50: 11 (nM) from 1 assay(s)
162	PDBBind: 1NZQ	IC50: 11 (nM) from 1 assay(s)

Biologically Interesting Molecules (External Reference) 1 Unique

Entity ID: 3
ID	Chains	Name	Type/Class	2D Diagram	3D Interactions
PRD_000480 Query on PRD_000480	C [auth D]	HIRUDIN ANALOGUE	Oligopeptide / Anticoagulant, Antithrombotic		Interactions Focus chain C [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.18 Å
R-Value Free: 0.242
R-Value Work: 0.197
R-Value Observed: 0.197
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 71.11	α = 90
b = 71.96	β = 100.82
c = 73.16	γ = 90

Software Package:

Software Name	Purpose
X-GEN	data scaling
X-GEN	data reduction
CNS	refinement
CNS	phasing

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2003-10-14

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2003-10-14
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: 2016-05-25
Changes: Source and taxonomy
Version 1.5: 2017-10-11
Changes: Refinement description
Version 1.6: 2018-04-04
Changes: Data collection