4DM3

Crystal structure of human PNMT in complex adohcy, resorcinol and imidazole

PDB DOI: https://doi.org/10.2210/pdb4DM3/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2012-02-06 Released: 2012-04-25
Deposition Author(s): Nair, P.C., Malde, A.K., Mark, A.E.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.40 Å
R-Value Free: 0.275
R-Value Work: 0.220
R-Value Observed: 0.223

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Re-refinement Note

This entry reflects an alternative modeling of the original data in: 3KPY

Literature

Missing fragments: detecting cooperative binding in fragment-based drug design.

Nair, P.C., Malde, A.K., Drinkwater, N., Mark, A.E.

(2012) ACS Med Chem Lett 3: 322-326

PubMed: 24900472 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/ml300015u
Primary Citation of Related Structures:
4DM3

PubMed Abstract:
The aim of fragment-based drug design (FBDD) is to identify molecular fragments that bind to alternate subsites within a given binding pocket leading to cooperative binding when linked. In this study, the binding of fragments to human phenylethanolamine N-methyltransferase is used to illustrate how (a) current protocols may fail to detect fragments that bind cooperatively, (b) theoretical approaches can be used to validate potential hits, and (c) apparent false positives obtained when screening against cocktails of fragments may in fact indicate promising leads.

Organizational Affiliation

School of Chemistry and Molecular Biosciences (SCMB) and Institute for Molecular Bioscience (IMB), The University of Queensland (UQ) , St Lucia Campus, Brisbane, QLD 4072, Australia.

Macromolecule Content

Total Structure Weight: 64.82 kDa
Atom Count: 4,394
Modelled Residue Count: 525
Deposited Residue Count: 578
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Phenylethanolamine N-methyltransferase	A, B	289	Homo sapiens	Mutation(s): 0 Gene Names: PNMT, PENT EC: 2.1.1.28
UniProt & NIH Common Fund Data Resources
Find proteins for P11086 (Homo sapiens) Explore P11086 Go to UniProtKB: P11086
PHAROS: P11086 GTEx: ENSG00000141744
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P11086
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SAH Query on SAH Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain F [auth B] MOL2 format, chain C [auth A] MOL2 format, chain F [auth B] mmCIF format, chain C [auth A] mmCIF format, chain F [auth B]	C [auth A], F [auth B]	S-ADENOSYL-L-HOMOCYSTEINE C₁₄ H₂₀ N₆ O₅ S ZJUKTBDSGOFHSH-WFMPWKQPSA-N		Interactions Focus chain C [auth A] Focus chain F [auth B] Interactions & Density Focus chain C [auth A] Focus chain F [auth B]
RCO Query on RCO Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain G [auth B] MOL2 format, chain D [auth A] MOL2 format, chain G [auth B] mmCIF format, chain D [auth A] mmCIF format, chain G [auth B]	D [auth A], G [auth B]	RESORCINOL C₆ H₆ O₂ GHMLBKRAJCXXBS-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain G [auth B] Interactions & Density Focus chain D [auth A] Focus chain G [auth B]
IMD Query on IMD Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain H [auth B] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B]	E [auth A], H [auth B]	IMIDAZOLE C₃ H₅ N₂ RAXXELZNTBOGNW-UHFFFAOYSA-O		Interactions Focus chain E [auth A] Focus chain H [auth B] Interactions & Density Focus chain E [auth A] Focus chain H [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
SAH	BindingDB: 4DM3	Ki: 1.40e+4 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.40 Å
R-Value Free: 0.275
R-Value Work: 0.220
R-Value Observed: 0.223
Space Group: P 4₃ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 93.908	α = 90
b = 93.908	β = 90
c = 188.615	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-04-25

Deposition Author(s):

Nair, P.C.

Malde, A.K.

Mark, A.E.

Revision History (Full details and data files)

Version 1.0: 2012-04-25
Type: Initial release
Version 1.1: 2014-09-17
Changes: Database references
Version 1.2: 2018-01-24
Changes: Advisory, Structure summary
Version 1.3: 2024-11-27
Changes: Advisory, Data collection, Database references, Derived calculations, Structure summary