6SAS

Human Carbonic Anhydrase II in complex with fragment.

PDB DOI: https://doi.org/10.2210/pdb6SAS/pdb

Classification: LYASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2019-07-17 Released: 2020-04-15
Deposition Author(s): Gloeckner, S., Heine, A., Klebe, G.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.10 ?
R-Value Free: 0.149
R-Value Work: 0.132
R-Value Observed: 0.133

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II.

Glockner, S., Heine, A., Klebe, G.

(2020) Biomolecules 10

PubMed: 32235320 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.3390/biom10040518
Primary Citation of Related Structures:
5M78, 6RM1, 6RMP, 6S9Z, 6SAC, 6SAS, 6SAY, 6SB7, 6SDJ

PubMed Abstract:
Fragment screening is a powerful tool to identify and characterize binding pockets in proteins. We herein present the results of a proof-of-concept screening campaign of a versatile 96-entry fragment library from our laboratory against the drug target and model protein human carbonic anhydrase II. The screening revealed a novel chemotype for carbonic anhydrase inhibition, as well as less common non-covalent interaction types and unexpected covalent linkages. Lastly, different runs of the PanDDA tool reveal a practical hint for its application.

Organizational Affiliation

Institute for Pharmaceutical Chemistry, Philipps-Universit?t Marburg, Marbacher Weg 6, 35037 Marburg, Germany.

Macromolecule Content

Total Structure Weight: 30.67 kDa
Atom Count: 2,524
Modelled Residue Count: 257
Deposited Residue Count: 265
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Carbonic anhydrase 2	A	265	Homo sapiens	Mutation(s): 0 Gene Names: CA2 EC: 4.2.1.1 (PDB Primary Data), 4.2.1.69 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P00918 (Homo sapiens) Explore P00918 Go to UniProtKB: P00918
PHAROS: P00918 GTEx: ENSG00000104267
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00918
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
BE7 Query on BE7 Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	(4-CARBOXYPHENYL)(CHLORO)MERCURY C₇ H₅ Cl Hg O₂ YFZOUMNUDGGHIW-UHFFFAOYSA-M		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
HG Query on HG Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A] mmCIF format, chain D [auth A]	D [auth A]	MERCURY (II) ION Hg BQPIGGFYSBELGY-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
463 (Subject of Investigation/LOI) Query on 463 Download Ideal Coordinates CCD File SDF format, chain F [auth A] MOL2 format, chain F [auth A] mmCIF format, chain F [auth A]	F [auth A]	N-[3-(aminomethyl)phenyl]acetamide C₉ H₁₂ N₂ O JLFWORHZSACMOG-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Interactions & Density Focus chain F [auth A]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.10 ?
R-Value Free: 0.149
R-Value Work: 0.132
R-Value Observed: 0.133
Space Group: P 1 2₁ 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 42.383	α = 90
b = 41.543	β = 104.334
c = 72.121	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data reduction
XDS	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2020-04-15

Deposition Author(s):

Gloeckner, S.

Heine, A.

Klebe, G.

Revision History (Full details and data files)

Version 1.0: 2020-04-15
Type: Initial release
Version 1.1: 2024-01-24
Changes: Data collection, Database references, Derived calculations, Refinement description