1N1M

Human Dipeptidyl Peptidase IV/CD26 in complex with an inhibitor

PDB DOI: https://doi.org/10.2210/pdb1N1M/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Trichoplusia ni
Mutation(s): No

Deposited: 2002-10-18 Released: 2002-12-27
Deposition Author(s): Rasmussen, H.B., Branner, S., Wiberg, F.C., Wagtmann, N.R.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.263
R-Value Work: 0.208
R-Value Observed: 0.211

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 2.1 of the entry. See complete history.

Literature

Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analogue

Rasmussen, H.B., Branner, S., Wiberg, F.C., Wagtmann, N.R.

(2003) Nat Struct Biol 10: 19-25

PubMed: 12483204 Search on PubMed
DOI: https://doi.org/10.1038/nsb882
Primary Citation of Related Structures:
1N1M

PubMed Abstract:
Dipeptidyl peptidase IV (DPP-IV/CD26) is a multifunctional type II transmembrane serine peptidase. This enzyme contributes to the regulation of various physiological processes, including blood sugar homeostasis, by cleaving peptide hormones, chemokines and neuropeptides. We have determined the 2.5 A structure of the extracellular region of DPP-IV in complex with the inhibitor valine-pyrrolidide. The catalytic site is located in a large cavity formed between the alpha/beta-hydrolase domain and an eight-bladed beta-propeller domain. Both domains participate in inhibitor binding. The structure indicates how substrate specificity is achieved and reveals a new and unexpected opening to the active site.

Organizational Affiliation

Protein Chemistry, Research and Development, Novo Nordisk A/S, Novo Allé, DK-2880 Bagsvaerd, Denmark. [email protected]

Macromolecule Content

Total Structure Weight: 176.12 kDa
Atom Count: 13,270
Modelled Residue Count: 1,454
Deposited Residue Count: 1,456
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Dipeptidyl peptidase IV SOLUBLE FORM	A, B	728	Homo sapiens	Mutation(s): 0 EC: 3.4.14.5
UniProt & NIH Common Fund Data Resources
Find proteins for P27487 (Homo sapiens) Explore P27487 Go to UniProtKB: P27487
PHAROS: P27487 GTEx: ENSG00000197635
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P27487
Glycosylation
Glycosylation Sites: 7	Glycosylation Focus chain A Focus chain B	Go to GlyGen: P27487-1
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

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Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose	C	3		N-Glycosylation	Interactions Focus chain C Interactions & Density Focus chain C
Glycosylation Resources
GlyTouCan: G19870TQ GlyCosmos: G19870TQ GlyGen: G19870TQ

Entity ID: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose	D	3		N-Glycosylation	Interactions Focus chain D Interactions & Density Focus chain D
Glycosylation Resources
GlyTouCan: G21290RB GlyCosmos: G21290RB GlyGen: G21290RB

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	E, G, H, J	2		N-Glycosylation	Interactions Focus chain E Focus chain G Focus chain H Focus chain J Interactions & Density Focus chain E Focus chain G Focus chain H Focus chain J
Glycosylation Resources
GlyTouCan: G42666HT GlyCosmos: G42666HT GlyGen: G42666HT

Entity ID: 5
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	F	3		N-Glycosylation	Interactions Focus chain F Interactions & Density Focus chain F
Glycosylation Resources
GlyTouCan: G52260VY GlyCosmos: G52260VY GlyGen: G52260VY

Entity ID: 6
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose	I	2		N-Glycosylation	Interactions Focus chain I Interactions & Density Focus chain I
Glycosylation Resources
GlyTouCan: G86851RC GlyCosmos: G86851RC GlyGen: G86851RC

Entity ID: 7
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	K, L	3		N-Glycosylation	Interactions Focus chain K Focus chain L Interactions & Density Focus chain K Focus chain L
Glycosylation Resources
GlyTouCan: G15407YE GlyCosmos: G15407YE GlyGen: G15407YE

Entity ID: 8
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	M	2		N-Glycosylation	Interactions Focus chain M Interactions & Density Focus chain M
Glycosylation Resources
GlyTouCan: G07375KG GlyCosmos: G07375KG GlyGen: G07375KG

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain N [auth A] SDF format, chain R [auth B] SDF format, chain S [auth B] MOL2 format, chain N [auth A] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] mmCIF format, chain N [auth A] mmCIF format, chain R [auth B] mmCIF format, chain S [auth B]	N [auth A], R [auth B], S [auth B]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain N [auth A] Focus chain R [auth B] Focus chain S [auth B] Interactions & Density Focus chain N [auth A] Focus chain R [auth B] Focus chain S [auth B]
HG Query on HG Download Ideal Coordinates CCD File SDF format, chain O [auth A] SDF format, chain P [auth A] SDF format, chain T [auth B] SDF format, chain U [auth B] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] mmCIF format, chain O [auth A] mmCIF format, chain P [auth A] mmCIF format, chain T [auth B] mmCIF format, chain U [auth B]	O [auth A], P [auth A], T [auth B], U [auth B]	MERCURY (II) ION Hg BQPIGGFYSBELGY-UHFFFAOYSA-N		Interactions Focus chain O [auth A] Focus chain P [auth A] Focus chain T [auth B] Focus chain U [auth B] Interactions & Density Focus chain O [auth A] Focus chain P [auth A] Focus chain T [auth B] Focus chain U [auth B]
A3M Query on A3M Download Ideal Coordinates CCD File SDF format, chain Q [auth A] SDF format, chain V [auth B] MOL2 format, chain Q [auth A] MOL2 format, chain V [auth B] mmCIF format, chain Q [auth A] mmCIF format, chain V [auth B]	Q [auth A], V [auth B]	2-AMINO-3-METHYL-1-PYRROLIDIN-1-YL-BUTAN-1-ONE C₉ H₁₈ N₂ O IHBAVXVTGLANPI-QMMMGPOBSA-N		Interactions Focus chain Q [auth A] Focus chain V [auth B] Interactions & Density Focus chain Q [auth A] Focus chain V [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
A3M	BindingDB: 1N1M	Ki: min: 470, max: 2000 (nM) from 2 assay(s)
	BindingDB: 1N1M	IC50: min: 548, max: 5400 (nM) from 4 assay(s)
	PDBBind: 1N1M	Ki: 2000 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.263
R-Value Work: 0.208
R-Value Observed: 0.211
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 119.234	α = 90
b = 123.448	β = 90
c = 131.315	γ = 90

Software Package:

Software Name	Purpose
MAR345	data collection
SCALEPACK	data scaling
SOLVE	phasing
CNX	refinement

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2002-12-27

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2002-12-27
Type: Initial release
Version 1.1: 2008-04-28
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Non-polymer description, Version format compliance
Version 1.3: 2017-10-11
Changes: Data collection, Refinement description
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
Version 2.1: 2024-10-30
Changes: Data collection, Database references, Structure summary