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Ho Leung Ng

Kansas State University, Biochemistry and Molecular Biophysics, Faculty Member

University of Hawaii at Manoa, Chemistry, Faculty Member

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Research in crystallography and computational structural biology as applied to structure based drug design of both small and protein therapeutics. Specific interests include membrane proteins, protein kinases, kinase receptors, GPCRs, fluorescent proteins. Applications of machine learning to drug discovery and chemistry.
Supervisors: David Eisenberg, Richard Dickerson, Tom Alber, and Brian Kobilka

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Papers by Ho Leung Ng

Saccharomyces cerevisiae septins: supramolecular organization of heterooligomers and the mechanism of filament assembly

by Patricia Grob and Ho Leung Ng

Proceedings of the …, Jan 1, 2008

Autofluorescent proteins with excitation in the optical window for intravital imaging in mammals

Chemistry & biology, Jan 1, 2009

Automated electron‐density sampling reveals widespread conformational polymorphism in proteins

Protein …, Jan 1, 2010

Moving Metal Ions through Ferritin− Protein Nanocages from Three-Fold Pores to Catalytic Sites

Journal of the American …, Jan 1, 2010

Allosteric Activation Mechanism of the Mycobacterium tuberculosis Receptor Ser/Thr Protein Kinase, PknB

Structure, Jan 1, 2010

Detecting protein function and protein-protein interactions from genome sequences

Science, Jan 1, 1999

The structure of a stable intermediate in the A↔ B DNA helix transition

Proceedings of the …, Jan 1, 2000

An alternate conformation and a third metal in PstP/Ppp, the M. tuberculosis PP2C-family Ser/Thr protein phosphatase

Structure, Jan 1, 2004

Mediation of the A/B‐DNA helix transition by G‐tracts in the crystal structure of duplex CATGGGCCCATG

Nucleic acids research, Jan 1, 2002

An unusual sugar conformation in the structure of an RNA/DNA decamer of the polypurine tract may affect recognition by RNase H

Journal of molecular …, Jan 1, 2003

Local conformational variations observed in B-DNA crystals do not improve base stacking: computational analysis of base stacking in ad (CATGGGCCCATG) 2 B↔ A …

Nucleic acids research, Jan 1, 2000

DNA structure from A to B

… Academy of Sciences of the United …, Jan 1, 2001

Saccharomyces cerevisiae septins: supramolecular organization of heterooligomers and the mechanism of filament assembly

Proceedings of the …, Jan 1, 2008

A conserved dimer and global conformational changes in the structure of apo-PknE Ser/Thr protein kinase from Mycobacterium tuberculosis

Journal of molecular biology, Jan 1, 2006

Sensor Domain of the Mycobacterium tuberculosis Receptor Ser/Thr Protein Kinase, PknD, forms a Highly Symmetric [beta] Propeller

Journal of molecular …, Jan 1, 2004

Mycobacterium tuberculosis protein tyrosine phosphatase PtpB structure reveals a diverged fold and a buried active site

Structure, Jan 1, 2005

Intracellular pathogenic bacteria manipulate host signal transduction pathways to facilitate infe... more Intracellular pathogenic bacteria manipulate host signal transduction pathways to facilitate infection. Mycobacterium tuberculosis protein tyrosine phosphatases (PTPs) PtpA and PtpB are thought to be secreted into host cells and interfere with unidentified signals. To illuminate the mechanisms of regulation and substrate recognition, we determined the 1.7 A resolution crystal structure of PtpB in complex with the product phosphate. The protein adopts a simplified PTP fold, which combines features of the conventional PTPs and dual-specificity phosphatases. PtpB shows two unusual elaborations--a disordered, acidic loop and a flexible, two-helix lid that covers the active site--that are specific to mycobacterial orthologs. Biochemical studies suggest that substrate mimicry in the lid may protect the phosphatase from oxidative inactivation. The insertion and deletion of large structural elements in PtpB suggest that, outside the active site module, the PTP family is under unusual selective pressure that promotes changes in overall structure.

Mildly eccentricE-DNA'

Nature Structural & Molecular Biology, Jan 1, 2001

Recently, the crystal structures of the DNA hexamers d (GGCGm 5 CC) 2 and d (GGCGBr 5 CC) 2, were... more Recently, the crystal structures of the DNA hexamers d (GGCGm 5 CC) 2 and d (GGCGBr 5 CC) 2, were reported by Vargason et al. 1 in Nature Structural Biology to adopt a novel extended and eccentric conformation which the authors call E-DNA. This new conformation has no connection with Struther Arnott&amp;amp;amp;#x27;s earlier E-DNA 2, proposed in 1980 from fiber studies, which is a member of the B family with a 48 twist angle. Like the previously reported crystal structure of d (CATGGGCCCATG) 2 (ref. 3), thenew&amp;amp;amp;#x27;E-DNA has some ...

Structure of a dicationic monoimidazole lexitropsin bound to DNA

Biochemistry, Jan 1, 1995

An X-ray crystal structure has been solved of the complex of a dicationic lexitropsin with a B-DN... more An X-ray crystal structure has been solved of the complex of a dicationic lexitropsin with a B-DNA duplex of sequence CGCGAATTCGCG. The lexitropsin is identical to netropsin except for replacement of the first methylpyrrole ring by methylimidazole, converting a =CH- to =N-. Crystals are isomorphous with those of the DNA dodecamer in the absence of drug. Although the =N- for =CH- substitution was intended to make that locus on the drug molecule compatible with a G.C base pair, electrostatic attraction for the two cationic ends of the drug predominates, and this lexitropsin binds to the same central AATT site as does the parent netropsin. But unlike netropsin, this lexitropsin exhibits end-for-end disorder in the crystal. Both orientations were refined separately to completion. Final residual errors at 2.25 A resolution for the 2358 reflections above 2 sigma in F are R = 0.165 for one orientation (LexA) with 37 water molecules and 0.164 for the inverted drug orientation (LexB) with 40 water molecules. This molecular disorder is probably attributable to a weakening of binding to the AATT site occasioned by the imidazole-for-pyrrole substitution.

Saccharomyces cerevisiae septins: supramolecular organization of heterooligomers and the mechanism of filament assembly

by Patricia Grob and Ho Leung Ng

Proceedings of the …, Jan 1, 2008

Autofluorescent proteins with excitation in the optical window for intravital imaging in mammals

Chemistry & biology, Jan 1, 2009

Automated electron‐density sampling reveals widespread conformational polymorphism in proteins

Protein …, Jan 1, 2010

Moving Metal Ions through Ferritin− Protein Nanocages from Three-Fold Pores to Catalytic Sites

Journal of the American …, Jan 1, 2010

Allosteric Activation Mechanism of the Mycobacterium tuberculosis Receptor Ser/Thr Protein Kinase, PknB

Structure, Jan 1, 2010

Detecting protein function and protein-protein interactions from genome sequences

Science, Jan 1, 1999

The structure of a stable intermediate in the A↔ B DNA helix transition

Proceedings of the …, Jan 1, 2000

An alternate conformation and a third metal in PstP/Ppp, the M. tuberculosis PP2C-family Ser/Thr protein phosphatase

Structure, Jan 1, 2004

Mediation of the A/B‐DNA helix transition by G‐tracts in the crystal structure of duplex CATGGGCCCATG

Nucleic acids research, Jan 1, 2002

An unusual sugar conformation in the structure of an RNA/DNA decamer of the polypurine tract may affect recognition by RNase H

Journal of molecular …, Jan 1, 2003

Local conformational variations observed in B-DNA crystals do not improve base stacking: computational analysis of base stacking in ad (CATGGGCCCATG) 2 B↔ A …

Nucleic acids research, Jan 1, 2000

DNA structure from A to B

… Academy of Sciences of the United …, Jan 1, 2001

Saccharomyces cerevisiae septins: supramolecular organization of heterooligomers and the mechanism of filament assembly

Proceedings of the …, Jan 1, 2008

A conserved dimer and global conformational changes in the structure of apo-PknE Ser/Thr protein kinase from Mycobacterium tuberculosis

Journal of molecular biology, Jan 1, 2006

Sensor Domain of the Mycobacterium tuberculosis Receptor Ser/Thr Protein Kinase, PknD, forms a Highly Symmetric [beta] Propeller

Journal of molecular …, Jan 1, 2004

Mycobacterium tuberculosis protein tyrosine phosphatase PtpB structure reveals a diverged fold and a buried active site

Structure, Jan 1, 2005

Intracellular pathogenic bacteria manipulate host signal transduction pathways to facilitate infe... more Intracellular pathogenic bacteria manipulate host signal transduction pathways to facilitate infection. Mycobacterium tuberculosis protein tyrosine phosphatases (PTPs) PtpA and PtpB are thought to be secreted into host cells and interfere with unidentified signals. To illuminate the mechanisms of regulation and substrate recognition, we determined the 1.7 A resolution crystal structure of PtpB in complex with the product phosphate. The protein adopts a simplified PTP fold, which combines features of the conventional PTPs and dual-specificity phosphatases. PtpB shows two unusual elaborations--a disordered, acidic loop and a flexible, two-helix lid that covers the active site--that are specific to mycobacterial orthologs. Biochemical studies suggest that substrate mimicry in the lid may protect the phosphatase from oxidative inactivation. The insertion and deletion of large structural elements in PtpB suggest that, outside the active site module, the PTP family is under unusual selective pressure that promotes changes in overall structure.

Mildly eccentricE-DNA'

Nature Structural & Molecular Biology, Jan 1, 2001

Recently, the crystal structures of the DNA hexamers d (GGCGm 5 CC) 2 and d (GGCGBr 5 CC) 2, were... more Recently, the crystal structures of the DNA hexamers d (GGCGm 5 CC) 2 and d (GGCGBr 5 CC) 2, were reported by Vargason et al. 1 in Nature Structural Biology to adopt a novel extended and eccentric conformation which the authors call E-DNA. This new conformation has no connection with Struther Arnott&amp;amp;amp;#x27;s earlier E-DNA 2, proposed in 1980 from fiber studies, which is a member of the B family with a 48 twist angle. Like the previously reported crystal structure of d (CATGGGCCCATG) 2 (ref. 3), thenew&amp;amp;amp;#x27;E-DNA has some ...

Structure of a dicationic monoimidazole lexitropsin bound to DNA

Biochemistry, Jan 1, 1995

An X-ray crystal structure has been solved of the complex of a dicationic lexitropsin with a B-DN... more An X-ray crystal structure has been solved of the complex of a dicationic lexitropsin with a B-DNA duplex of sequence CGCGAATTCGCG. The lexitropsin is identical to netropsin except for replacement of the first methylpyrrole ring by methylimidazole, converting a =CH- to =N-. Crystals are isomorphous with those of the DNA dodecamer in the absence of drug. Although the =N- for =CH- substitution was intended to make that locus on the drug molecule compatible with a G.C base pair, electrostatic attraction for the two cationic ends of the drug predominates, and this lexitropsin binds to the same central AATT site as does the parent netropsin. But unlike netropsin, this lexitropsin exhibits end-for-end disorder in the crystal. Both orientations were refined separately to completion. Final residual errors at 2.25 A resolution for the 2358 reflections above 2 sigma in F are R = 0.165 for one orientation (LexA) with 37 water molecules and 0.164 for the inverted drug orientation (LexB) with 40 water molecules. This molecular disorder is probably attributable to a weakening of binding to the AATT site occasioned by the imidazole-for-pyrrole substitution.