5N5J | pdb_00005n5j

Human MMP12 in complex with 3-(5-(1,2-dithiolan-3-yl)pentanamido)propane-1-sulfonate

PDB DOI: https://doi.org/10.2210/pdb5N5J/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2017-02-14 Released: 2017-11-01
Deposition Author(s): Calderone, V.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free:
0.195 (Depositor), 0.200 (DCC)
R-Value Work:
0.125 (Depositor), 0.140 (DCC)
R-Value Observed:
0.129 (Depositor)

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Lipoyl-Homotaurine Derivative (ADM_12) Reverts Oxaliplatin-Induced Neuropathy and Reduces Cancer Cells Malignancy by Inhibiting Carbonic Anhydrase IX (CAIX).

Fragai, M., Comito, G., Di Cesare Mannelli, L., Gualdani, R., Calderone, V., Louka, A., Richichi, B., Francesconi, O., Angeli, A., Nocentini, A., Gratteri, P., Chiarugi, P., Ghelardini, C., Tadini-Buoninsegni, F., Supuran, C.T., Nativi, C.

(2017) J Med Chem 60: 9003-9011

PubMed: 29048889 Search on PubMed
DOI: https://doi.org/10.1021/acs.jmedchem.7b01237
Primary Citation of Related Structures:
5N5J, 5N5K

PubMed Abstract:
Oxaliplatin (OXA) is a valuable and largely used cancer drug which induces a serious and intractable neuropathy. The lipoyl-homotaurine derivative (ADM_12) reverts in vivo OXA-induced neuropathy, and it is an effective antagonist of the nociceptive sensor channel TRPA1. Unprecedentedly, this safe analgesic showed a synergy with OXA in vitro and proved to inhibit CA IX, a relevant therapeutic target, clearly interfering with pancreatic cancer cells' aggressiveness.

Organizational Affiliation

Department of Chemistry, University of Florence , via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy.

Macromolecule Content

Total Structure Weight: 18.14 kDa
Atom Count: 1,408
Modelled Residue Count: 158
Deposited Residue Count: 158
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Macrophage metalloelastase	A	158	Homo sapiens	Mutation(s): 1 Gene Names: MMP12, HME EC: 3.4.24.65
UniProt & NIH Common Fund Data Resources
Find proteins for P39900 (Homo sapiens) Explore P39900 Go to UniProtKB: P39900
PHAROS: P39900 GTEx: ENSG00000262406
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P39900
Sequence Annotations Expand
Reference Sequence LOADING

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
8NT Query on 8NT Download Ideal Coordinates CCD File SDF format, chain H [auth A] MOL2 format, chain H [auth A] mmCIF format, chain H [auth A]	H [auth A]	3-[5-[(3~{S})-1,2-dithiolan-3-yl]pentanoylamino]propane-1-sulfonic acid C₁₁ H₂₁ N O₄ S₃ SZYIEKXYLQGLFW-JTQLQIEISA-N		Interactions Focus chain H [auth A] Interactions & Density Focus chain H [auth A]
HAE Query on HAE Download Ideal Coordinates CCD File SDF format, chain G [auth A] MOL2 format, chain G [auth A] mmCIF format, chain G [auth A]	G [auth A]	ACETOHYDROXAMIC ACID C₂ H₅ N O₂ RRUDCFGSUDOHDG-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Interactions & Density Focus chain G [auth A]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain B [auth A] SDF format, chain C [auth A] MOL2 format, chain B [auth A] MOL2 format, chain C [auth A] mmCIF format, chain B [auth A] mmCIF format, chain C [auth A]	B [auth A], C [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Focus chain C [auth A] Interactions & Density Focus chain B [auth A] Focus chain C [auth A]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A]	D [auth A], E [auth A], F [auth A]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.195 (Depositor), 0.200 (DCC)
R-Value Work: 0.125 (Depositor), 0.140 (DCC)
R-Value Observed: 0.129 (Depositor)

Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 50.926	α = 90
b = 60.47	β = 114.55
c = 53.844	γ = 90

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: 2017-11-01

Deposition Author(s):

Calderone, V.

Revision History (Full details and data files)

Version 1.0: 2017-11-01
Type: Initial release
Version 1.1: 2017-11-22
Changes: Database references
Version 1.2: 2024-01-17
Changes: Data collection, Database references, Refinement description