2C0T

Src family kinase Hck with bound inhibitor A-641359

PDB DOI: https://doi.org/10.2210/pdb2C0T/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): Yes

Deposited: 2005-09-07 Released: 2006-09-20
Deposition Author(s): Borhani, D.W., Burchat, A., Calderwood, D.J., Hirst, G.C., Li, B., Loew, A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.253
R-Value Work: 0.194
R-Value Observed: 0.197

Starting Model: experimental
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Ligand Structure Quality Assessment

This is version 1.5 of the entry. See complete history.

Literature

Discovery of A-770041, a Src-Family Selective Orally Active Lck Inhibitor that Prevents Organ Allograft Rejection.

Burchat, A., Borhani, D.W., Calderwood, D.J., Hirst, G.C., Li, B., Stachlewitz, R.F.

(2006) Bioorg Med Chem Lett 16: 118

PubMed: 16216497 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2005.09.039
Primary Citation of Related Structures:
2C0I, 2C0O, 2C0T

PubMed Abstract:
We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days.

Organizational Affiliation

Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605-5314, USA.

Macromolecule Content

Total Structure Weight: 105.32 kDa
Atom Count: 7,225
Modelled Residue Count: 858
Deposited Residue Count: 908
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
TYROSINE-PROTEIN KINASE HCK	A, B	454	Homo sapiens	Mutation(s): 3 EC: 2.7.1.112 (PDB Primary Data), 2.7.10.2 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P08631 (Homo sapiens) Explore P08631 Go to UniProtKB: P08631
PHAROS: P08631 GTEx: ENSG00000101336
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P08631
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
L3G Query on L3G 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]	N-(4-{4-AMINO-1-[1-(TETRAHYDRO-2H-PYRAN-4-YL)PIPERIDIN-4-YL]-1H-PYRAZOLO[3,4-D]PYRIMIDIN-3-YL}-2-METHOXYPHENYL)-1-METHYL-1H-INDOLE-2-CARBOXAMIDE C₃₂ H₃₆ N₈ O₃ CMFPSTWYLODPNE-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain F [auth B] Interactions & Density Focus chain C [auth A] Focus chain F [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain G [auth B] SDF format, chain H [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain G [auth B] mmCIF format, chain H [auth B]	D [auth A], E [auth A], G [auth B], H [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain G [auth B] Focus chain H [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain G [auth B] Focus chain H [auth B]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
PTR Query on PTR	A, B	L-PEPTIDE LINKING	C₉ H₁₂ N O₆ P		TYR

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.253
R-Value Work: 0.194
R-Value Observed: 0.197
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 48.861	α = 90
b = 72.909	β = 95.87
c = 180.002	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
HKL-2000	data reduction
SCALEPACK	data scaling
AMoRE	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2006-09-20

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2006-09-20
Type: Initial release
Version 1.1: 2011-07-13
Changes: Advisory, Version format compliance
Version 1.2: 2019-03-06
Changes: Data collection, Derived calculations, Experimental preparation, Other
Version 1.3: 2019-05-08
Changes: Data collection, Experimental preparation
Version 1.4: 2023-12-13
Changes: Data collection, Database references, Derived calculations, Other, Refinement description
Version 1.5: 2024-10-16
Changes: Structure summary