4CDF

Human DPP1 in complex with (2S,4S)-N-((1S)-1-cyano-2-(4-(4- cyanophenyl)phenyl)ethyl)-4-hydroxy-piperidine-2-carboxamide

PDB DOI: https://doi.org/10.2210/pdb4CDF/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2013-10-31 Released: 2014-03-19
Deposition Author(s): Debreczeni, J., Edman, K., Furber, M., Tiden, A., Gardiner, P., Mete, T., Ford, R., Millichip, I., Stein, L., Mather, A., Kinchin, E., Luckhurst, C., Cage, P., Sanghanee, H., Breed, J., Wissler, L.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.20 Å
R-Value Free: 0.255
R-Value Work: 0.217
R-Value Observed: 0.219

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Cathepsin C Inhibitors: Property Optimization and Identification of a Clinical Candidate.

Furber, M., Gardiner, P., Tiden, A.K., Mete, A., Ford, R., Millichip, I., Stein, L., Mather, A., Kinchin, E., Luckhurst, C., Barber, S., Cage, P., Sanganee, H., Austin, R., Chohan, K., Beri, R., Thong, B., Wallace, A., Oreffo, V., Hutchinson, R., Harper, S., Debreczeni, J., Breed, J., Wissler, L., Edman, K.

(2014) J Med Chem 57: 2357

PubMed: 24592859 Search on PubMed
DOI: https://doi.org/10.1021/jm401705g
Primary Citation of Related Structures:
4CDC, 4CDD, 4CDE, 4CDF

PubMed Abstract:
A lead generation and optimization program delivered the highly selective and potent CatC inhibitor 10 as an in vivo tool compound and potential development candidate. Structural studies were undertaken to generate SAR understanding.

Organizational Affiliation

AstraZeneca , Pepparedsleden 1, Mölndal 431 83, Sweden.

Macromolecule Content

Total Structure Weight: 81.56 kDa
Atom Count: 5,786
Modelled Residue Count: 699
Deposited Residue Count: 710
Unique protein chains: 3

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
DIPEPTIDYL PEPTIDASE 1 EXCLUSION DOMAIN CHAIN	A, D	120	Homo sapiens	Mutation(s): 0 EC: 3.4.14.1
UniProt & NIH Common Fund Data Resources
Find proteins for P53634 (Homo sapiens) Explore P53634 Go to UniProtKB: P53634
PHAROS: P53634 GTEx: ENSG00000109861
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P53634
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
DIPEPTIDYL PEPTIDASE 1 HEAVY CHAIN	B, E	166	Homo sapiens	Mutation(s): 0 EC: 3.4.14.1
UniProt & NIH Common Fund Data Resources
Find proteins for P53634 (Homo sapiens) Explore P53634 Go to UniProtKB: P53634
PHAROS: P53634 GTEx: ENSG00000109861
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P53634
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
DIPEPTIDYL PEPTIDASE 1 LIGHT CHAIN	C, F	69	Homo sapiens	Mutation(s): 0 EC: 3.4.14.1
UniProt & NIH Common Fund Data Resources
Find proteins for P53634 (Homo sapiens) Explore P53634 Go to UniProtKB: P53634
PHAROS: P53634 GTEx: ENSG00000109861
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P53634
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
W2C Query on W2C Download Ideal Coordinates CCD File SDF format, chain I [auth B] SDF format, chain M [auth E] MOL2 format, chain I [auth B] MOL2 format, chain M [auth E]	I [auth B], M [auth E]	(2S,4S)-N-[(2S)-1-azanylidene-3-[4-(4-cyanophenyl)phenyl]propan-2-yl]-4-oxidanyl-piperidine-2-carboxamide C₂₂ H₂₄ N₄ O₂ IOCQAXABAZCRSK-QCXLXSPFSA-N		Interactions Focus chain I [auth B] Focus chain M [auth E] Interactions & Density Focus chain I [auth B] Focus chain M [auth E]
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain H [auth B] SDF format, chain K [auth D] SDF format, chain L [auth E] MOL2 format, chain G [auth A] MOL2 format, chain H [auth B] MOL2 format, chain K [auth D] MOL2 format, chain L [auth E]	G [auth A], H [auth B], K [auth D], L [auth E]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain G [auth A] Focus chain H [auth B] Focus chain K [auth D] Focus chain L [auth E] Interactions & Density Focus chain G [auth A] Focus chain H [auth B] Focus chain K [auth D] Focus chain L [auth E]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain J [auth B] SDF format, chain N [auth E] MOL2 format, chain J [auth B] MOL2 format, chain N [auth E]	J [auth B], N [auth E]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain J [auth B] Focus chain N [auth E] Interactions & Density Focus chain J [auth B] Focus chain N [auth E]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.20 Å
R-Value Free: 0.255
R-Value Work: 0.217
R-Value Observed: 0.219
Space Group: P 3₁ 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 84.85	α = 90
b = 84.85	β = 90
c = 222.452	γ = 120

Software Package:

Software Name	Purpose
REFMAC	refinement
MOSFLM	data reduction
SCALA	data scaling
MOLREP	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2014-03-19

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2014-03-19
Type: Initial release
Version 1.1: 2014-04-09
Changes: Database references
Version 1.2: 2019-04-24
Changes: Data collection, Derived calculations, Other, Source and taxonomy
Version 1.3: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Data collection, Derived calculations, Other, Structure summary
Version 1.4: 2023-12-20
Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary