Oligomeric Proteins Animation

Specificity of Enzyme Action Lecture

Induced Fit Model Animation

In 1958 Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continually reshaped by interactions with the substrate as the substrate interacts with the enzyme.As a result, the substrate does not simply bind to a rigid active site; the amino acid side chains which make up the active site are molded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases, the substrate molecule also changes shape slightly as it enters the active site. The active site continues to change until the substrate is completely bound, at which point the final shape and charge is determined.

Enzyme - Lock & Key Mechnaism Animation

Enzymes are very specific, and it was suggested by Emil Fischer in 1894 that this was because both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. This is often referred to as "the lock and key" model. However, while this model explains enzyme specificity, it fails to explain the stabilization of the transition state that enzymes achieve. The "lock and key" model is therefore less accurate than the induced fit model.

Imaging Patients with Myelopathy

Nancy Fischbein, MD, associate professor of neurosurgery, discusses the challenges of assessing spinal cord injury and the latest imaging techniques for diagnosis.

Homeodomain Animation

The homeodomain fold is a protein structural domain that binds DNA or RNA and is thus commonly found in transcription factors.The fold consists of a 60-amino acid helix-turn-helix structure in which three alpha helices are connected by short loop regions. The N-terminal two helices are antiparallel and the longer C-terminal helix is roughly perpendicular to the axes established by the first two. It is this third helix that interacts directly with DNA. Homeodomain folds are found exclusively in eukaryotes but have high homology to lambda phage proteins that alter the expression of genes in prokaryotes. Many homeodomains induce cellular differentiation by initiating the cascades of coregulated genes required to produce individual tissues and organs, while homeodomain proteins like Nanog are involved in maintaning pluripotency.

Homeobox genes
The homeobox is a stretch of DNA about 180 nucleotides long that encodes a homeodomain. Homeobox genes code for homeodomain proteins in both vertebrates and invertebrates. The existence of homeoboxes was first discovered in Drosophila, where the radical alterations that resulted from mutations in homeobox genes were termed homeotic mutations. The most famous such mutation is Antennapedia, in which legs grow from the head of a fly instead of the expected antennae. Homeobox genes are critical in the establishment of body axes during embryogenesis.

The consensus 60-polypeptide chain is [1](typical intron position noted with dashes)


The motif is highly conserved over hundreds of millions of years of evolutionary history, with typically 80% match in the corresponding nucleotide sequence to the consensus sequence across species, genera and phyla.

Sequence specificity

Homeodomains can bind both specifically and nonspecifically to B-DNA with the C-terminal recognition helix aligning in the DNA's major groove and the unstructured peptide "tail" at the N-terminus aligning in the minor groove. The recognition helix and the inter-helix loops are rich in arginine and lysine residues, which form hydrogen bonds to the DNA backbone; conserved hydrophobic residues in the center of the recognition helix aid in stabilizing the helix packing. Homeodomain proteins show a preference for the DNA sequence 5'-ATTA-3'; sequence-independent binding occurs with significantly lower affinity.

POU proteins

Proteins containing a POU region consist of a homeodomain and a separate, structurally homologous POU domain that contains two helix-turn-helix motifs and also binds DNA. The two domains are linked by a flexible loop that is long enough to stretch around the DNA helix, allowing the two domains to bind on opposite sides of the target DNA, collectively covering an eight-base segment with consensus sequence 5'-ATGCAAAT-3'. The individual domains of POU proteins bind DNA only weakly, but have strong sequence-specific affinity when linked. Interestingly, the POU domain itself has significant structural similarity with repressors expressed in bacteriophages, particularly lambda phage.

Dlx proteins

Vertebrates have six genes from the Dlx family of homeodomain transcription factors, arranged into three clusters: Dlx1/Dlx2, Dlx3/Dlx4 and Dlx5/Dlx6. All six are homologs of the fly gene Distal-less. Dlx genes are involved in the development of the nervous system and of limbs.

Intimate Encounters with Molecules: Taming Molecular Wildness


Athetosis is a continuous stream of slow, sinuous, writhing movements, typically of the hands and feet. Movements typical to athetosis are sometimes called athetoid movements. It is said to be caused by damage to the corpus striatum of the brain - specifically to the putamen. It can also be caused by a lesion of the motor thalamus

Structural Biology and Structure Based Ligand Video


Craig Venter unveils "Synthetic life"

Craig Venter and team make a historic announcement: they've created the first fully functioning, reproducing cell controlled by synthetic DNA. He explains how they did it and why the achievement marks the beginning of a new era for science.

About Speaker;
Craig Venter, the man who led the private effort to sequence the human genome, is hard at work now on even more potentially world-changing projects.

First, there's his mission aboard the Sorcerer II, a 92-foot yacht, which, in 2006, finished its voyage around the globe to sample, catalouge and decode the genes of the ocean's unknown microorganisms. Quite a task, when you consider that there are tens of millions of microbes in a single drop of sea water. Then there's the J. Craig Venter Institute, a nonprofit dedicated to researching genomics and exploring its societal implications.

In 2005, Venter founded Synthetic Genomics, a private company with a provocative mission: to engineer new life forms. Its goal is to design, synthesize and assemble synthetic microorganisms that will produce alternative fuels, such as ethanol or hydrogen. He was on Time magzine's 2007 list of the 100 Most Influential People in the World.

In early 2008, scientists at the J. Craig Venter Institute announced that they had manufactured the entire genome of a bacterium by painstakingly stitching together its chemical components. By sequencing a genome, scientists can begin to custom-design bootable organisms, creating biological robots that can produce from scratch chemicals humans can use, such as biofuel. And in 2010, they announced, they had created "synthetic life" -- DNA created digitally, inserted into a living bacterium, and remaining alive.

HIV and flu -- the vaccine strategy

Seth Berkley explains how smart advances in vaccine design, production and distribution are bringing us closer than ever to eliminating a host of global threats -- from AIDS to malaria to flu pandemics.